C-Fos
Encyclopedia
In the field of molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

 and Genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

, c-Fos is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 encoded by the FOS gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Structure and function

c-Fos is a cellular proto-oncogene belonging to the immediate early gene
Immediate early gene
Immediate early genes are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized...

 family of transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

s. c-Fos has a leucine-zipper DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 binding domain, and a transactivation
Transactivation
In molecular biology and genetics, transactivation is an increased rate of gene expression triggered either by biological processes or by artificial means.- Natural transactivation :...

 domain at the C-terminus. Transcription of c-Fos is upregulated in response to many extracellular signals, e.g., growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....

s. In addition, phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 by MAPK
Mitogen-activated protein kinase
Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...

, PKA, PKC
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...

 or cdc2 alters the activity and stability of c-Fos. Members of the Fos family dimerise with C-jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...

 to form the AP-1 transcription factor, which upregulates transcription of a diverse range of genes involved in everything from proliferation and differentiation to defense against invasion and cell damage.

Clinical significance

The AP-1 complex has been implicated in transformation and progression of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, and both Fos and Jun were first discovered in rat fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

s. Fos was discovered as the transforming gene of the FBJ MSV and jun, first as the Fos-binding protein p39, then subsequently as the oncogene from avian sarcoma virus 17 (junana = 17).

The viral homologue
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

 of c-Fos, v-Fos, is found in the retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...

 Finkel–Biskis–Jinkins murine osteogenic sarcoma virus.

At least one study has shown that acute treatment with LSD is linked with a marked upregulation of c-fos expression in mammals.

Applications

Neuroscientists measure expression of c-fos as an indirect marker of neuronal activity because c-fos is often expressed when neurons fire action potentials. Upregulation of c-fos mRNA in a neuron indicates recent activity.

Interactions

C-Fos has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with CSNK2A2
CSNK2A2
Casein kinase II subunit alpha is an enzyme that in humans is encoded by the CSNK2A2 gene.-Interactions:CSNK2A2 has been shown to interact with CSNK2B, FGF1, PTEN, RELA, ATF1, Nucleolin, CREB binding protein, Activating transcription factor 2, PIN1, C-jun and C-Fos.-Further reading:...

, Casein kinase 2, alpha 1, BCL3
BCL3
B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin...

, DNA damage-inducible transcript 3
DNA damage-inducible transcript 3
DNA damage-inducible transcript 3 is a protein that in humans is encoded by the DDIT3 gene.-Interactions:DNA damage-inducible transcript 3 has been shown to interact with Casein kinase 2, alpha 1, JunD, RPS3A, ATF3, CEBPB, C-jun and C-Fos....

, Cofactor of BRCA1
Cofactor of BRCA1
Cofactor of BRCA1, also known as COBRA1, is a human gene that encodes NELF-B. NELF-B is a subunit of negative elongation factor , which also includes NELF-A , either NELF-C or NELF-D , and NELF-E...

, TATA binding protein
TATA Binding Protein
The TATA-binding protein is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 35 base pairs upstream of the transcription start site in some eukaryotic gene promoters...

, RELA
RELA
Transcription factor p65 is a protein that in humans is encoded by the RELA gene.-Interactions:RELA has been shown to interact with NFKBIB, ETHE1, NFKBIE, RFC1, TRIB3, CREB binding protein, Neutrophil cytosolic factor 1, Glucocorticoid receptor, MTPN, BRCA1, C-Fos, POU2F1, BTRC, TATA-binding...

, Nuclear receptor coactivator 1
Nuclear receptor coactivator 1
The nuclear receptor coactivator 1 is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity . NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates...

, Nuclear receptor co-repressor 2
Nuclear receptor co-repressor 2
The nuclear receptor co-repressor 2 is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target...

, RUNX2
Runx2
Runt-related transcription factor 2 also known as core-binding factor subunit alpha-1 is a protein that in humans is encoded by the RUNX2 gene RUNX2 is a key transcription factor associated with osteoblast differentiation....

, RUNX1
RUNX1
Runt-related transcription factor 1 also known as acute myeloid leukemia 1 protein or core-binding factor subunit alpha-2 is a protein that in humans is encoded by the RUNX1 gene....

, C-jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...

 and Mothers against decapentaplegic homolog 3
Mothers against decapentaplegic homolog 3
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins.The human SMAD3 gene is located on chromosome 15...

.

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