What is the difference between a protein and a factor?

What is the difference between a protein and a factor?

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In terms of nomenclature/semantics, why are some proteins named proteins, and some named factors?

I've been revising on eukaryotic DNA, and I've come across some proteins that seem to serve roughly the same function, but are named differently. For example,

  • Replication activator protein
  • Replication licensing factors
  • Replication protein A
  • Replication factor C
  • Transcriptional factor
  • Eukaryotic translation initiation factor

TLDR: As far as I know, there's no specific reason some proteins are called "factors"; it's just a matter of what name was chosen.

"Protein" is a specific term meaning a long chain of amino acids. They are typically at least 50 amino acids long.

Conversely, the word "factor" is quite a loose term and is as broad as even being "an element of something". So, essentially anything in biology from a chemical to temperature could be called a factor.

In the context of biochemistry, a factor is a "substance which takes part in a biochemical reaction… … or process". This could include everything from proteins and enzymes (e.g. EGF), to non-protein chemicals such as substrates, co-factors. Even Ca$^{2+}$ (coagulation factor IV) and nitric oxide/arachidonic acid/etc. (EDHF) fall under this umbrella - a single ion is about as far from a protein as it's possible to get! So many proteins are also given the label of "factor". In fact, Protein C has been named both "Protein C" and "blood coagulation factor XIV".

One reason various proteins have been called "factors" is that the word factor used to be used to refer to genes. I'd speculate that another reason may be that certain names and acronyms were already in place. For example, protein C vs. factor C or CREB-binding protein (CBP) vs. core binding factor (CBF).

But as long as the naming of the proteins is standardized, I see no reason why we shouldn't just use acronyms to describe proteins. After all, protein names can be misleading (e.g. Sonic Hedgehog), and there is a large amount of confusion in the literature between names of proteins.

Short Answer

There is no agreed upon naming convention for proteins - there are some rough standards because in language people usually try to convey their ideas in a way others can understand, but that doesn't necessarily mean fixed rules.

Longer Answer

I think it's important to recognize the process for understanding what proteins do is not always straightforward. Most often, a protein's function is first understood by seeing what happens if that protein is absent (and sometimes overexpressed).

The terminology factor implies that a protein is either modulating a process or at least is not by itself sufficient for a process. That is, it is named because when it was omitted, some other measurable process changed. It maybe implies something that has its main function by binding, rather than catalyzing a chemical reaction, or at least that the actual mechanism of action is not yet known at the time of naming.

You would not expect, for example, an enzyme with a known target to be called a factor: it's most likely to be named according to its target and the type of reaction being catalyzed.

However, it's possible for a name to stick from when there is less complete understanding. Something might be called a factor initially because of how it influences some process, but the actual contribution is only understood later. Just for an example, take Complement factor I. Initially named because it had some role in the complement system, now it's known that it enzymatically cleaves another protein.

Importantly, there isn't any pure terminology here or consistent naming convention: in most cases, it just goes back to however the first person to describe the protein discussed it. Some proteins are named (controversially, I'll add) things like Sonic hedgehog - related to the similarly named Hedgehog signalling pathway which is all named because of one person/group's creative description of a related fruit fly phenotype.

Naming something "protein" just identifies that it's a protein, little more.

Short Answer
All factors are proteins, not all proteins are factors

A factor is typically a small protein that regulates a larger target protein directly by specifically associating with it, or indirectly by affecting its substrate. For example, protein factors play key roles in protein synthesis (Berg et al., 2002) and see Fig. 1.:

  • An initiation factor binds to the much larger and more complex multi-subunit ribosome during the initiation of translation, a part of protein biosynthesis (fig. 1);
  • A release factor terminates translation by the ribosome by recognizing the termination codon or stop codon in an mRNA sequence
  • A transcription factor is a protein that regulates the much more complex and bigger RNA polymerase. Transcription factors control the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence.

-Berg et al., Biochemistry, 5th ed. New York: Freeman (2002)

Fig. 1. Inititation factors are relatively small proteins that interact with the large ribosomal multi-subunit complex. source: Concepts Of Genetics

There are at least two reasons why certain compounds were historically named in the manner 'function-factor'.

  1. When you have some impure preparation that exerts a biological function but do not know the chemical nature of the component responsible is.

For example an unknown growth factor, could be a protein, but it could also be a steroid etc.

  1. As a deliberate contrast to enzyme to emphasize that the activity is not catalytic. The point here is not the opposition to a different type of protein.

For example, in DNA or RNA synthesis you have the actual enzymes (DNA and RNA polymerases) that work catalytically to form phosphodiester bonds, and then various accessory proteins that are required to bind to specific regions of DNA, but do not catalyse any chemical reaction. In this case the word 'protein' does not distinguish the molecule from an enzyme.

In cases where the need to make such distinctions is not evident to a scientist who has established the protein nature of an activity, he may have chosen to designate it protein for greater precision.


When a field has matured sufficiently there is often an initiative to rationalize nomenclature. This is frequently resisted by the originators of the nomenclature. In this respect Fritz Lipmann is reputed to have said that “changing names is rewriting history”.

Difference between Cofactor and Coenzyme

The difference between cofactor and coenzyme is mainly due to the following factors:
Chemical nature: Cofactors constitutes a large group of helper molecules that can be inorganic and organic, while cofactors are simply the small, organic molecules.
Function: Coenzymes significantly acts as a carrier material to convert the inactive protein (Apoenzyme) into the active form (Holoenzyme). In contrast, cofactors only fasten the enzymatic reaction inside a cell.

Both cofactor and coenzyme are important terms to study the chemical and physical properties of an enzyme. It is important to note that the cofactors or coenzymes only attach to the types of conjugated enzymes that also contain a non-protein region. Hence, the simple enzymes that entirely contains amino acids do not require any additional carriers to show its catalytic activity.

Good Proteins Vs. Bad Proteins

Getting a lean body and Kevlar-like abs doesn't happen automatically. It takes hard work and time spent at the gym, as well as a diet rich in protein.

As long as it's the right kind of protein.

Everyone knows that fats are bad and that carbohydrates are suspect, but protein can do no wrong--or so we thought. While many proteins are good, there are some that can be bad for your health.

Since the late 1990s, the Atkins diet, and other fads, like the South Beach diet, have popularized high-protein, low-carb meal plans. As a result, consumption of protein-rich foods has risen dramatically. The Nutrition Business Journal in San Diego estimated that in 2004, Americans spent about $1.2 billion on protein supplements, and an additional $2 billion on protein bars. The Department of Commerce reports that per capita consumption of fish is up 4.5%--as is beef consumption, which rose 25% between 1998 and 2004, according to the National Cattleman's Beef Association.

But not all beef is the same: There is a world of difference between a fatty cheeseburger and a lean sirloin steak. But Americans are still making unhealthy dietary decisions. In fact, people in the U.S. have never been less healthy. With almost 70% of the population overweight, it seems people are more confused than informed about what they should be eating.

First, we all know that protein is supposed to be good for us, but what does it do exactly? Protein is essential for a balanced diet, because it builds muscle and collagen. According to the director of health promotion & communication at Harvard University, Dr. Lilian Cheung, protein is the building block of enzymes, hormones, immune factors and many other molecules that are critical to the body. Harvard's online magazine, Nutrition Source, states, "Adults need a minimum of one gram of protein for every kilogram of body weight per day to keep from slowly breaking down their own tissues."

That means a person who weighs 140 pounds should consume about 63 grams of protein per day--the equivalent of two large chicken fillets--which, for most people, isn't a problem. Weight loss stems from a process called ketosis, which is the basis for the Atkins diet, in which, if all of the starch is removed from one's diet, the body will begin to release fat--instead of storing it--and then burn it as fuel. But that doesn't mean that the more protein you eat, the more fat you lose, because, in the end, protein still contains calories--even in small amounts--and once it turns into fat, the body won't be able to burn all of it at once. Losing weight is about expending more calories than you consume.

The United States Department of Agriculture says the average American already consumes more than enough protein--sometimes much more, although there are no studies that indicate too much protein is bad for you. What can be bad, however, is how you ingest that protein. After all, any food consumed in excess--whether a protein, carbohydrate or fat--is unhealthy.

The trick is learning the good proteins from the bad, and how much you need.

"What makes a protein good is its nutrient base, how it was raised and farmed, its omega-3 fatty acid value and if it's high or low in saturated fat," says Oz Garcia, nutritionist and author of Look and Feel Fabulous Forever. Omega-3 fatty acids are a type of polyunsaturated fat--a good fat--found primarily in fish, which has healing properties for patients with heart disease.

Soy-based products are surprisingly controversial. While soya-based products used to be primarily for strict vegetarians and the lactose-intolerant, it has now taken its place in the dairy aisle as a type of 'super food,' because it is a vegetable-based protein that packs plenty of nutrients. Soya is making its way into more items than just soy milk, and some nutritionists warn that having too much could have hormone-altering side effects. That's because soya contains phytochemicals and phytoestrogen, which are great for women undergoing menopause, but not so great for the average person.

The best way to stay healthy is with a balanced diet--one that provides adequate amounts of essential nutrients and leaves a person feeling satisfied after they eat. In fact, most foods naturally combine protein, carbs and fat, which is why a low-carb or no-carb diet is unrealistic.

"I tell my clients that one cup of cooked rice has five grams of protein, even though we think of rice as a 'carb' food, and that spaghetti has about seven grams of protein," says Anne Collins, a nutritionist and founder of "This is why I strongly advocate a balanced diet."

Which is great news for red-meat lovers--as well as for fish fanatics and egg enthusiasts--because a healthy diet doesn't have to be restricted to chicken breasts and grain burgers. Grilling a lean slab of beef tenderloin without heavy sauce or greasy sides is a good way to get protein. And though eggs have been frowned upon in the past, they can actually be a good addition to a diet, as long as the yolk, which contains the bulk of fat and cholesterol, is removed.

To find out more about which proteins are good--and bad--for you, follow the links below.

4 Levels of Protein Structure (With Diagram)

By convention, four levels of protein organization may be identified these are called the primary, secondary, tertiary, and quaternary structures of the protein.

1. Primary Protein Structure:

Successive amino acids forming the backbone of a polypeptide chain are linked together through peptide bonds and it is believed that these are the only covalent associations that occur between successive amino acids.

The primary structure of a protein is the order of these amino acids in the backbone of each of the polypeptide chains comprising the molecule.

The primary structure of a polypeptide chain is de­lineated beginning with the amino acid occupying the polypeptide’s N-terminus. For convenience, each amino acid is identified using its specific abbreviation. The first protein to have its primary structure determined was the hormone insulin, a rela­tively small protein containing only 51 amino acids.

The insulin molecule consists of two polypeptide chains called the A chain (21 amino acids long) and the B chain (30 amino acids long). The structure of insulin is shown in Figure 4-16 and reveals yet another facet of the covalent associations that can exist in proteins.

The A and B chains of insulin are linked together by two disulfide bridges and a third disulfide bridge oc­curs within the A chain. As shown in Figure 4-17, disulfide bridges are formed by the removal of hydro­gen from the sulfhydryl groups of the side chains of two cysteine residues.

When the primary structure of a polypeptide chain is determined chemically, it is cus­tomary to simultaneously determine which cysteine residues of the structure are involved in the formation of disulfide bridges.Since the elucidation of the primary structure of in­sulin in 1953 by F. Sanger (for which Sanger received a Nobel Prize), several hundred proteins have been fully sequenced, many of these considerably larger than insulin. Among the fully sequenced proteins are nearly 100 forms of hemoglobin, the oxygen- transporting protein in the blood of vertebrates.

Stud­ies of hemoglobin have revealed some fascinating facts concerning the evolution of related proteins and the manner in which different polypeptide chains of a pro­tein interact with one another in the molecule’s biolog­ical activity.

Inherent Variety of Protein Primary Structures:

The di­versity of amino acids that may be included in proteins provides for an enormous number of different pri­mary structures. Consider, for example, the mathe­matical variety that is possible in a polypeptide chain consisting of 61 amino acids (and this would be consid­ered a relatively small protein). Each of the 61 residue positions can be occupied by any one of 20 different amino acids.

Therefore, altogether there would be 20 61 possible polypeptide molecules (i.e., 20 61 different pri­mary structures are possible). Now, 20 61 = 2.3x 10 79 , and because it has been estimated that the entire uni­verse contains 0.9 x 10 79 atoms, there is greater poten­tial variety in a polypeptide chain that is 61 amino ac­ids long than there are atoms in the universe!

Secondary Protein Structure:

When describing a protein’s primary structure, the order of amino acids in each polypeptide chain but not the resulting three-dimensional shape is considered. The three-dimensional shape is taken into account be­ginning with secondary structure.

A protein’s sec­ondary structure describes any periodic spatial rela­tionships within each of the polypeptide chains, such as:

(1) The locations and extent of those regions of each chain that are organized into helices and

(2) The type of helices that are present.

Among the periodic structures that are common in polypeptide chains are the alpha, pi, and 310 helices discussed earlier and the various beta conformations. In globular proteins, it is not uncommon for half of all the residues of each polypeptide to be organized into one or more specific secondary structures.

For convenience the various segments of a polypep­tide chain can be assigned a specific nomenclature. Beginning at the N-terminus, the helical regions are denoted by the letters A, B, C, D, and so on, and the amino acids within each helix are assigned numbers (e.g., C1, C2, C3, etc.). The inter-helical regions of each chain are denoted by the letters of the adjoining heli­ces (i.e., non-helical regions AB, BC, CD, etc.) and the amino acids within these regions are also assigned numbers (i.e., BC1, BC2, BC3, etc.).

The non-helical region at the N-terminus (if indeed the N-terminus is not part of a helix) is denoted NA and its amino acids are numbered consecutively (NA1, NA2, NA3, etc.). If there is a non-helical segment at the C-terminus, it is identified on the basis of the last helix. For example, in a polypeptide chain containing eight helices (A through H), a non-helical segment at the C-terminus would be identified as HC (and its amino acids num­bered HC1, HC2, HC3, etc.). Using this type of no­menclature, the specific position of any amino acid can be identified (see Fig. 4-18).

Tertiary Protein Structure:

Tertiary protein structure refers to the manner in which the helical and non-helical regions of a polypep­tide are folded back on themselves to add yet another order of shape to the molecule. In globular proteins, it is the non-helical regions that permit the folding. The folding of a polypeptide chain is not random but oc­curs in a specific fashion, thereby imparting certain steric properties to the protein.

Well before the three- dimensional atomic structure of the first protein was worked out, W. Kauzmann anticipated the general principles that would govern the overall shape of a pro­tein. Kauzmann predicted in 1959 that all polar groups in the protein would either interact with each other or be solvated by the surrounding water and those considerations of entropy would draw the nonpolar parts of the protein together in the molecule’s interior.

This kind of specific folding is achieved and maintained by a variety of interactions between one part of the polypeptide chain and another and between the polypeptide and neighboring mole­cules of water.

The interactions include:

(1) Ionic bonds or salt bridges,

Ionic Bonds (Salt Bridges):

In aqueous solutions, most amino acids occur in an ionized (or dissociated) state. For example, most molecules of glycine exist in the following form when glycine is dissolved in water:

In this form, a hydrogen ion (i.e., a proton) has been dissociated from the α-carboxyl group and another has been removed from the surrounding water by the a-amino group. The resulting ion is called a zwitterion because it bears two different kinds of charge—positive and negative. Note that while having both kinds of charge the glycine molecule has no net charge.

The acidic amino acid aspartic acid has the follow­ing zwitterionic form:

In this case, aspartic acid bears one positive charge and two negative charges and thus has a net charge (i.e., -1). Glutamic acid behaves in a similar manner.

Finally, the basic amino acid lysine yields the follow­ing zwitterion in solution:

In this form, lysine carries two positive charges and one negative charge and has a net positive charge (i.e., +1).

In polypeptide chains, the a-amino and a-carboxyl groups of all of the amino acids except those that are at the n- and c-terminals are involved in peptide link­ages. Therefore, except at the ends of the polypeptide chain, these groups are not ionized and contribute no charge to the polypeptide.

However, the side chains of acidic and basic amino acids (as well as certain others) may contribute positive and negative charges along the length of the polypeptide if either conditions of lo­cal pH or the nature of the other side chains in the re­gion of the tertiary structure allow dissociation or protonation.

Electrostatic attraction between oppo­sitely charged side chains of amino acids of a polypep­tide may bring these regions of the chain closer to­gether and stabilize their positions relative to one another. The bonds so formed are called ionic bonds or salt bridges (also salt bonds).

It is also possible for ionized side chains of amino acids in the interior of the molecule to react with and bind water, and in many proteins a certain quantity of water is permanently re­tained within the molecule by such interactions. Be­cause salt ions (e.g., Na + and Cl – ) are also present in the surroundings of most proteins, these may also play a role in ionic bond formation between different ionized groups in the interior of the molecule. Ionic bonds also occur between charged side chains that project from the protein’s surface and surrounding water and salt ions. The various kinds of ionic bonds are shown in Figure 4-19.

Hydrogen bonds formed between a-amino hydrogen atoms and a-carboxyl oxygen at­oms have already been discussed in connection with the stabilization of helices and parallel chains of the beta pleated sheet structure. Hydrogen bonds can also be formed between un-dissociated carboxyl- containing side chains of the acidic amino acids and the amino groups of the basic amino acids lysine, tryptophan, and histidine.

The hydroxyl groups of serine, theonine, and tyrosine may also participate in hydrogen bonding, as may the secondary carboxyl and amino groups of asparagine and glutamine. Although individually weak, these bonds collectively contribute to the stability of a specific tertiary structure.

Third classes of interactions that stabilize tertiary protein structure are hydro­phobic bonds. These are interactions between amino acids whose side chains are hydrophobic (e.g., leucine, isoleucine, valine, and the aromatic amino acids).

The side chains of these amino acids are drawn together by their mutual hydrophobic properties, becoming organ­ized in such a manner as to have minimal contact with the surrounding water. Placed in close proximity to one another, juxtaposed atoms of separate side chains undergo van der Waals interactions with each other, resulting in the formation of weak bonds.

Again, it is the large numbers of these interactions that impart stability to the structure. Figure 4-20 depicts the sta­bilization of a fold in a polypeptide chain by the hydro­phobic association between two valine side chains.

Because they are covalent, disul­fide bridges are the strongest bonds formed between one part of a polypeptide chain and another. The nature and formation of these bonds have already been discussed in connection with primary protein structure (see above). Such bonds can be formed be­tween cysteine residues in different regions of a poly­peptide (and also between cysteine residues in differ­ent polypeptide chains of a protein, see below). Where they occur, disulfide bridges contribute a considerable stabilizing influence to tertiary structure.

The four classes of bonds just discussed are de­picted together in the generalized tertiary protein structure diagrammed in Figure 4-21. As you exam­ine this diagram, it is important to note that bonds stabilizing tertiary folding may simultaneously stabi­lize secondary structure.

For example, the disulfide bridge and the hydrophobic and electrostatic bonds that keep the top and middle helices of the protein de­picted in Figure 4-21 parallel to each other also serve to prevent unwinding of these two helices. Thus, in a general sense, specific interactions between one part of a protein and another can play a stabilizing role at more than one level of the protein’s structure.

Quaternary Protein Structure:

Many proteins consist of more than one polypeptide chain. In proteins that are composed of two or more polypeptide chains, the quaternary structure refers to the specific orientation of these chains with respect to one another and the nature of the interactions that stabilize this orientation. The individual polypeptide chains of the protein are usually referred to as its sub- units. Table 4-4 lists some representative proteins that are composed of subunits and gives their num­bers, designations, and molecular weights.

As can be seen from this sampling, proteins can contain either a small number of large subunits (e.g., thyroglobuliri), a large number of small subunits (e.g., apoferritin), or any intermediate combination. Moreover, in some proteins the subunits are polypeptide chains whose primary structures are identical to each other (e.g., L-arabinose isomerase), whereas in others the subu­nits are different (e.g., immunoglobulin G).

The same classes of interactions that contribute to the stability of tertiary protein structure also serve to stabilize the quaternary association of subunits, namely, ionic bonds, hydrogen bonds, hydrophobic bonds, and disulfide bridges. Many cellular enzymes are composed of subunits, and the resulting quaternary structure is of fundamental importance in the regulation of enzyme activity.

The molecular weights of proteins composed of subunits are often great enough for the molecules to be seen and studied by electron micros­copy of negatively stained preparations. Electron mi­croscopy thus provides additional information about quaternary structure, for it is often possible to discern the number and orientation of the protein’s subunits. The subunit organization of the enzyme L-arabinose isomerase is quite evident in the electron photomicro­graphs of Figure 4-22.

Among the groups of proteins whose quaternary structures have been extensively studied are the hemoglobin’s and immunoglobulin’s. Probably more is known about the chemistry, organization, and func­tions of members of these two groups than about all other proteins combined.

What Is the Difference Between a Peptide and a Protein?

Proteins and peptides are fundamental components of cells that carry out important biological functions. Proteins give cells their shape, for example, and they respond to signals transmitted from the extracellular environment. Certain types of peptides play key roles in regulating the activities of other molecules. Structurally, proteins and peptides are very similar, being made up of chains of amino acids that are held together by peptide bonds (also called amide bonds). So, what distinguishes a peptide from a protein?

The basic distinguishing factors are size and structure. Peptides are smaller than proteins. Traditionally, peptides are defined as molecules that consist of between 2 and 50 amino acids, whereas proteins are made up of 50 or more amino acids. In addition, peptides tend to be less well defined in structure than proteins, which can adopt complex conformations known as secondary, tertiary, and quaternary structures. Functional distinctions may also be made between peptides and proteins.

There are agricultural applications too

While the stability of peptides is a challenge to be overcome in human use, it’s a double-edged sword, and may be an advantage in some agricultural uses. The speed of degradation of peptides used as insecticides or fungicides means that they are not going to persist in the environment.

So creating greater stability of peptides can work both ways.

If the stability of the peptide can be tailored, then it can be made to last long enough to work on the crop, but then also to degrade.

This means it would not cause the long-term problems of DDT, for example, which can exist for hundreds of years.


Plant materials and growth conditions

Nicotiana benthamiana seeds were provided by College of Life Sciences, Wuhan University, China. The Nicotiana benthamiana used in this study were grown in the greenhouse under artificial light to maintain a 16 h light and 8 h darkness photoperiod at 22 ± 2 °C. For the BiFC experiments, the leaves of 5-week-old plants were used.

Phylogenetic analysis

The protein sequences of PCNA1/2 in Arabidopsis and PCNA in rice were identified through using the Arabidopsis Information Resource (TAIR) database ( and the National Center for Biotechnology Information (NCBI) database (, respectively. The sequences of AtPCNA1/2 and OsPCNA were used to search for PCNA homologs in other species. Multiple sequence alignment was performed using the DNAMAN software. A neighbor-joining tree was constructed using the MEGA4 software.

Quantitative real-time PCR

Total RNA from various tissues was extracted by RNAiso Plus (TaKaRa, Japan).

Quantitative Real-Time PCR (qRT-PCR) was carried out using TransStart Eco qPCR SuperMix (TransGen, China) in a BIO-RAD CFX Connect machine (BIO-RAD, USA). At least three biological replicates were performed for each gene, and at least three technical replicates were performed for each biological replicate. The method for analyzing the relative expression levels is the △ △ Ct method [50], and the GAPDH and Actin were applied as reference genes for Arabidopsis and rice PCNA genes in qRT-PCR analysis, respectively.

Construction of vectors for yeast-two-hybrid and BiFC analysis

To construct the vectors for Y2H analysis, the full-length open reading frames (ORFs) of AtRFC1/2/3/4/5, OsRFC1/2/3/4/5, AtPCNA1/2 and OsPCNA with stop codon were amplified with the help of KOD-Plus-Neo polymerase (TOYOBO, using specific primers (Additional file 9). Then, the PCR products were purified using an AxyPrep™ PCR Cleanup Kit (Axygen, and cloned into the pGADT7 and pGBKT7 vectors, respectively. Similarly, the full-length open reading frames (ORFs) of AtRFC1/2/3/4/5, OsRFC1/2/3/4/5, AtPCNA1/2 and OsPCNA were amplified and cloned into the pCAMBIA-SPYNE and pCAMBIA-SPYCE vectors for BiFC assay.

Yeast-two-hybrid analysis

A yeast-two-hybrid system (Clontech, was used to test interactions between AtPCNA1/2 and AtRFC1/2/3/4/5, OsPCNA and OsRFC1/2/3/4/5 proteins. The AH109 yeast strain was transformed with appropriate combinations of bait and prey plasmids along with negative control vectors. After transformation, the yeast cells were transferred onto SD-Leu-Trp selection plates followed by a 3-day incubation at 28 °C. The transformed cells were plated on an SD-Leu-Trp-His-Ade solid medium, and incubated for 7 days at 28 °C before analysis.

BiFC assay

The BiFC analysis was performed as described previously [51]. Fluorescent signals of YFP were observed under an Olympus FluoView FV1000 confocal microscope to determine whether the two designate proteins could interact with each other. Under the confocal microscope (OLYMPUS Fluoview 1000), YFP signal was excited with an argon laser at a wavelength of 515 nm and emissed at wavelength of between 505 nm and 530 nm.

Accession numbers

The accession numbers of genes used in this study are: AtRFC1 (At5g22010), AtRFC2 (At1g63160), AtRFC3 (At1g77470), AtRFC4 (At1g21690), AtRFC5 (At5g27740), AtPCNA1 (At1g07370), AtPCNA2 (At2g29570), OsRFC1 (Os11g0572100), OsRFC2 (Os12g0176500), OsRFC3 (Os02g0775200), OsRFC4 (Os04g0569000), OsRFC5 (Os03g0792600), OsPCNA (Os02g0805200). The accession numbers of proteins used in this study are: AtPCNA1 (NP_172217.1), AtPCNA2 (NP_180517.1), OsPCNA (XP_015627245.1), HsPCNA (CAG38740.1), ScPCNA (NP_009645.1), ZmPCNA (NP_001105461.1), BnPCNA (NP_001303041.1), CePCNA (NP_500466.3), DmPCNA (XP_002091715.2), DrPCNA (NP_571479.2), GhPCNA (XP_016740519.1), GmPCNA (NP_001241553.1), MmPCNA (NP_035175.1), NbPCNA (CAA10108.1), and PtPCNA (XP_002298328.1).

What are Growth Factors?(Growth Factor Definition)

Growth factors, which generally considered as a subset of cytokines, refer to the diffusible signaling proteins that stimulate cell growth, differentiation, survival, inflammation, and tissue repair. They can be secreted by neighboring cells, distant tissues and glands, or even tumor cells themselves. Normal cells show a requirement for several growth factors to maintain proliferation and viability. Growth advantage is often found for the cells which secrete a growth factor.

Growth factor can exert their stimulation though endocrine, paracrine or autocrine mechanisms. Due to their short half-lives and slow diffusion in intercellular spaces, growth factors usually act locally. Typically, the signal transduction of growth factors is initiated by binding to their receptors on the surface of target cells. The specific instruction conveyed by a growth factor to a particular subpopulation of cells depends on the type of receptors, number of target cell, and the intracellular signal transduction subsequent to factor binding. Moreover, external factors such as the binding ability of a growth factor to extracellular matrices (ECM), ECM degradation, and concentration of the growth factor may have an effect on the ultimate response of a target cell to a specific growth factor.


GM-CSF is a monomeric glycoprotein that functions as a cytokine — it is a white blood cell growth factor. [6] GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection.

GM-CSF also has some effects on mature cells of the immune system. These include, for example, enhancing neutrophil migration and causing an alteration of the receptors expressed on the cells surface. [7]

GM-CSF signals via signal transducer and activator of transcription, STAT5. [8] In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity. [9] Thus, GM-CSF facilitates development of the immune system and promotes defense against infections.

GM-CSF also plays a role in embryonic development by functioning as an embryokine produced by reproductive tract. [10]

The human gene has been localized in close proximity to the interleukin 3 gene within a T helper type 2-associated cytokine gene cluster at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. GM-CSF and IL-3 are separated by an insulator element and thus independently regulated. [11] Other genes in the cluster include those encoding interleukins 4, 5, and 13. [12]

Human granulocyte-macrophage colony-stimulating factor is glycosylated in its mature form.

GM-CSF was first cloned in 1985, and soon afterwards three potential drug products were being made using recombinant DNA technology: molgramostim was made in Escherichia coli and is not glycosylated, sargramostim was made in yeast, has a leucine instead of proline at position 23 and is somewhat glycosylated, and regramostim was made in Chinese hamster ovary cells (CHO) and has more glycosylation than sargramostim. The amount of glycosylation affects how the body interacts with the drug and how the drug interacts with the body. [13]

At that time, Genetics Institute, Inc. was working on molgramostim, [14] Immunex was working on sargramostim (Leukine), [15] and Sandoz was working on regramostim. [16]

Molgramostim was eventually co-developed and co-marketed by Novartis and Schering-Plough under the trade name Leucomax for use in helping white blood cell levels recover following chemotherapy, and in 2002 Novartis sold its rights to Schering-Plough. [17] [18]

Sargramostim was approved by the US FDA in 1991 to accelerate white blood cell recovery following autologous bone marrow transplantation under the trade name Leukine, and passed through several hands, ending up with Genzyme, [19] which was subsequently acquired by Sanofi. Leukine is now owned by Partner Therapeutics (PTx).

Imlygic was approved by the US FDA in October 2015, [20] and in December 2015 by the EMA, as an oncolytic virotherapy, commercialized by Amgen Inc. This oncolytic herpes virus, named Talimogene laherparepvec, has been genetically engineered to express human GM-CSF using the tumor cells machinery. [21]

GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF as a biological target may reduce the inflammation or damage. Some drugs (e.g. otilimab) are being developed to block GM-CSF. [22] In critically ill patients GM-CSF has been trialled as a therapy for the immunosuppression of critical illness, and has shown promise restoring monocyte [23] and neutrophil [24] function, although the impact on patient outcomes is currently unclear and awaits larger studies.

GM-CSF stimulates monocytes and macrophages to produce pro-inflammatory cytokines, including CCL17. [25] Elevated GM-CSF has been shown to contribute to inflammation in inflammatory arthritis, osteoarthritis, colitis asthma, obesity, and COVID-19. [25] [26] [27]

Monoclonal antibodies against GM-CSF are being used as treatment in clinical trials against rheumatoid arthritis, ankylosing spondylitis, and COVID-19. [25]

What is the difference between mRNA and viral vector-based vaccines?

TORONTO -- After the National Advisory Committee on Immunization recently doubled down on its recommendation that mRNA vaccines are “preferred” over their viral vector-based counterparts in the fight against COVID-19, questions have been raised about the vaccines’ differences.

So far, Health Canada has currently authorized the use of four different COVID-19 vaccines made by Pfizer-BioNTech, Moderna, AstraZeneca, and Janssen (Johnson & Johnson’s vaccine division).

The Pfizer-BioNTech and Moderna vaccines use mRNA technology while the AstraZeneca and single-dose J&J shots are considered viral vector-based vaccines.

So what is the difference between mRNA and viral vector-based vaccines and why is NACI recommending one type over the other?


Viral vector-based vaccines, such as those developed by AstraZeneca and Johnson & Johnson, use a harmless virus, or adenovirus, as a delivery system to trigger the immune system to create antibodies to fight off an infection by SARS-CoV-2, which is the virus that causes COVID-19.

The adenovirus is not SARS-CoV-2 itself, but rather a different, harmless virus that has been manipulated so it’s unable to replicate and cause illness.

Adenoviruses are viruses that cause the common cold and there are many different types, which have been used for decades to deliver instructions for proteins, Health Canada explains on its website.

In the case of COVID-19, the vector virus delivers specific genetic instructions to the cells in the body to produce a harmless piece of SARS-CoV-2 called the spike protein. The cells then display this spike protein and the immune system triggers a response.

As a result, the immune system produces antibodies to the specific spike protein in order to fight off what it thinks is an infection. If the immune system encounters the real SARS-CoV-2 virus and its spike proteins, it will already be prepared to launch a defence against it.

The viral vector-based vaccines are genetically modified so they’re unable to replicate, which means once the antibodies are created, the viral vector is cleared for good.

According to the U.S. Centers for Disease Control and Prevention (CDC), the benefit of viral vector-based vaccines is that they provide protection against SARS-CoV-2 without ever having to risk the serious consequences of getting sick with COVID-19.

The CDC also stressed that these types of vaccines cannot cause an infection of COVID-19 or with the adenovirus being used as a vaccine vector.


For their COVID-19 vaccines, Pfizer-BioNTech and Moderna use a novel technology that has never been approved for widespread use before the pandemic.

This technology uses messenger ribonucleic acid (mRNA), which is a molecule that provides cells with genetic instructions for making proteins that are needed for numerous cellular functions in the body, including for energy and immune defence.

In a lab, scientists develop synthetic mRNA that is able to instruct the body’s cells to develop that same distinctive spike protein from the SARS-CoV-2 virus that the viral vector-based vaccines also target.

After the piece of protein is made, the cell breaks down the genetic instructions and gets rid of them. Both Health Canada and the CDC stressed that the mRNA never enters the central part of the cell where a person’s DNA material is located, which means the vaccine does not affect or interact with DNA in any way.

Like with the viral vector-based vaccines, the immune system identifies the foreign spike proteins produced by the cells and initiates an immune response by building antibodies against them. If the immune system faces the real SARS-CoV-2 virus, it will be ready to fight it off.

While there are similarities in how both mRNA and viral vector-based vaccines instruct cells to create the SARS-CoV-2 spike protein, mRNA vaccines differ in that they don’t contain any live virus.


The viral vector-based COVID-19 vaccines developed by AstraZeneca and Johnson & Johnson have been linked to an extremely rare and potentially life-threatening blood-clotting syndrome called vaccine-induced thrombotic thrombocytopenia (VITT) – which is the combination of low platelet counts with blood clots.

The risk for developing this syndrome is estimated to be anywhere from one case in 100,000 doses to one case in 250,000.

In Canada, there have been only seven reported VITT cases in all of the approximately 1.7 million doses of AstraZeneca that have been administered in the country so far.

Due to the extremely low risk of developing VITT after vaccination with a viral vector-based vaccine, however, NACI recently reaffirmed that the mRNA vaccines are “preferred” over the other ones and that it might be in the best interest of some Canadians who have a low risk of exposure to COVID-19 to wait for an mRNA dose.

Despite this guidance, both Health Canada and NACI have emphasized that the vaccines by AstraZeneca and Johnson & Johnson are safe and effective for the majority of the population and there could be far worse consequences of contracting COVID-19.


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