c-Fos

FBJ murine osteosarcoma viral oncogene homolog
PDB rendering based on 1a02.
Available structures PDB 1A02, 1FOS, 1S9K
Identifiers
Symbols	FOS; AP-1; C-FOS
External IDs	OMIM: 164810 MGI: 95574 HomoloGene: 3844 GeneCards: FOS Gene
Gene Ontology Molecular function • double-stranded DNA binding • sequence-specific DNA binding transcription factor activity • protein binding • sequence-specific DNA binding • transcription regulatory region DNA binding • protein dimerization activity • R-SMAD binding Cellular component • nucleus • nucleoplasm • transcription factor complex • nucleolus • synaptosome Biological process • conditioned taste aversion • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • DNA methylation • transcription, DNA-dependent • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • inflammatory response • transforming growth factor beta receptor signaling pathway • nervous system development • female pregnancy • aging • Toll signaling pathway • response to cold • response to light stimulus • response to mechanical stimulus • response to gravity • response to toxin • response to organic cyclic compound • sleep • cellular response to extracellular stimulus • response to lipopolysaccharide • response to progesterone stimulus • cellular response to hormone stimulus • response to cytokine stimulus • toll-like receptor 1 signaling pathway • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • cellular response to reactive oxygen species • response to drug • innate immune response • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • regulation of sequence-specific DNA binding transcription factor activity • stress-activated MAPK cascade • response to corticosterone stimulus • response to cAMP • response to protein stimulus • SMAD protein signal transduction • cellular response to calcium ion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2353	14281
Ensembl	ENSG00000170345	ENSMUSG00000021250
UniProt	P01100	P01101
RefSeq (mRNA)	NM_005252.3	NM_010234.2
RefSeq (protein)	NP_005243.1	NP_034364.1
Location (UCSC)	Chr 14: 75.75 – 75.75 Mb	Chr 12: 86.81 – 86.82 Mb
PubMed search	[1]	[2]

In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.^[1][2][3]

Structure and function

c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at the C-terminus. Transcription of c-Fos is upregulated in response to many extracellular signals, e.g., growth factors. In addition, phosphorylation by MAPK, PKA, PKC or cdc2 alters the activity and stability of c-Fos. Members of the Fos family dimerise with C-jun 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, and both Fos and Jun were first discovered in rat fibroblasts. 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 of c-Fos, v-Fos, is found in the retrovirus 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.^[4]

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.^[5] Upregulation of c-fos mRNA in a neuron indicates recent activity.^[6]

Interactions

C-Fos has been shown to interact with CSNK2A2,^[7] Casein kinase 2, alpha 1,^[7] BCL3,^[8] DNA damage-inducible transcript 3,^[9] Cofactor of BRCA1,^[10] TATA binding protein,^[11] RELA,^[12] Nuclear receptor coactivator 1,^[13][14] Nuclear receptor co-repressor 2,^[15] RUNX2,^[16][17] RUNX1,^[16][17] C-jun^{[12][18][19][20][21][22][23]} and Mothers against decapentaplegic homolog 3.^[24]

See also

• Leptomycin
• c-Jun
• Egr-1

References

1. ^ Monje P, Hernández-Losa J, Lyons RJ, Castellone MD, Gutkind JS (October 2005). "Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1". J. Biol. Chem. 280 (42): 35081–4. doi:10.1074/jbc.C500353200. PMID 16123044. 
2. ^ Bossis G, Malnou CE, Farras R, Andermarcher E, Hipskind R, Rodriguez M, Schmidt D, Muller S, Jariel-Encontre I, Piechaczyk M (August 2005). "Down-Regulation of c-Fos/c-Jun AP-1 Dimer Activity by Sumoylation". Mol. Cell. Biol. 25 (16): 6964–79. doi:10.1128/MCB.25.16.6964-6979.2005. PMC 1190241. PMID 16055710. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1190241. 
3. ^ Konsman JP, Blomqvist A (May 2005). "Forebrain patterns of c-Fos and FosB induction during cancer-associated anorexia-cachexia in rat". Eur. J. Neurosci. 21 (10): 2752–66. doi:10.1111/j.1460-9568.2005.04102.x. PMID 15926923. 
4. ^ Nichols CD, Sanders-Bush E (May 2002). "A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain". Neuropsychopharmacology 26 (5): 634–42. doi:10.1016/S0893-133X(01)00405-5. PMID 11927188. 
5. ^ VanElzakker M, Fevurly RD, Breindel T, Spencer RL (2008). "Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex". Learn. Mem. 15 (12): 899–908. doi:10.1101/lm.1196508. PMC 2632843. PMID 19050162. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2632843. 
6. ^ Day HE, Kryskow EM, Nyhuis TJ, Herlihy L, Campeau S (September 2008). "Conditioned Fear Inhibits c-fos mRNA Expression in the Central Extended Amygdala". Brain Res. 1229: 137–46. doi:10.1016/j.brainres.2008.06.085. PMC 2605076. PMID 18634767. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2605076. 
7. ^ ^{a b} Yamaguchi, Y; Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H (Aug. 1998). "Casein kinase II interacts with the bZIP domains of several transcription factors". Nucleic Acids Res. (ENGLAND) 26 (16): 3854–61. doi:10.1093/nar/26.16.3854. PMC 147779. PMID 9685505. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147779. 
8. ^ Na, S Y; Choi J E, Kim H J, Jhun B H, Lee Y C, Lee J W (Oct. 1999). "Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation". J. Biol. Chem. (UNITED STATES) 274 (40): 28491–6. doi:10.1074/jbc.274.40.28491. PMID 10497212. 
9. ^ Ubeda, M; Vallejo M, Habener J F (Nov. 1999). "CHOP Enhancement of Gene Transcription by Interactions with Jun/Fos AP-1 Complex Proteins". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7589–99. PMC 84780. PMID 10523647. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84780. 
10. ^ Zhong, Hongjun; Zhu Jianhua, Zhang Hao, Ding Lihua, Sun Yan, Huang Cuifen, Ye Qinong (Dec. 2004). "COBRA1 inhibits AP-1 transcriptional activity in transfected cells". Biochem. Biophys. Res. Commun. (United States) 325 (2): 568–73. doi:10.1016/j.bbrc.2004.10.079. PMID 15530430. 
11. ^ Metz, R; Bannister A J, Sutherland J A, Hagemeier C, O'Rourke E C, Cook A, Bravo R, Kouzarides T (Sep. 1994). "c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein". Mol. Cell. Biol. (UNITED STATES) 14 (9): 6021–9. PMC 359128. PMID 8065335. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359128. 
12. ^ ^{a b} Yang, X; Chen Y, Gabuzda D (Sep. 1999). "ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-kappaB". J. Biol. Chem. (UNITED STATES) 274 (39): 27981–8. doi:10.1074/jbc.274.39.27981. PMID 10488148. 
13. ^ Lee, S K; Na S Y, Jung S Y, Choi J E, Jhun B H, Cheong J, Meltzer P S, Lee Y C, Lee J W (Jun. 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. (UNITED STATES) 14 (6): 915–25. doi:10.1210/me.14.6.915. PMID 10847592. 
14. ^ Lee, S K; Kim H J, Na S Y, Kim T S, Choi H S, Im S Y, Lee J W (Jul. 1998). "Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits". J. Biol. Chem. (UNITED STATES) 273 (27): 16651–4. doi:10.1074/jbc.273.27.16651. PMID 9642216. 
15. ^ Lee, S K; Kim J H, Lee Y C, Cheong J, Lee J W (Apr. 2000). "Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor". J. Biol. Chem. (UNITED STATES) 275 (17): 12470–4. doi:10.1074/jbc.275.17.12470. PMID 10777532. 
16. ^ ^{a b} Hess, J; Porte D, Munz C, Angel P (Jun. 2001). "AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element". J. Biol. Chem. (United States) 276 (23): 20029–38. doi:10.1074/jbc.M010601200. PMID 11274169. 
17. ^ ^{a b} D'Alonzo, Richard C; Selvamurugan Nagarajan, Karsenty Gerard, Partridge Nicola C (Jan. 2002). "Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation". J. Biol. Chem. (United States) 277 (1): 816–22. doi:10.1074/jbc.M107082200. PMID 11641401. 
18. ^ Ito, T; Yamauchi M, Nishina M, Yamamichi N, Mizutani T, Ui M, Murakami M, Iba H (Jan. 2001). "Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers". J. Biol. Chem. (United States) 276 (4): 2852–7. doi:10.1074/jbc.M009633200. PMID 11053448. 
19. ^ Pognonec, P; Boulukos K E, Aperlo C, Fujimoto M, Ariga H, Nomoto A, Kato H (May. 1997). "Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity". Oncogene (ENGLAND) 14 (17): 2091–8. doi:10.1038/sj.onc.1201046. PMID 9160889. 
20. ^ Glover, J N; Harrison S C (Jan. 1995). "Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA". Nature (ENGLAND) 373 (6511): 257–61. doi:10.1038/373257a0. PMID 7816143. 
21. ^ Nomura, N; Zu Y L, Maekawa T, Tabata S, Akiyama T, Ishii S (Feb. 1993). "Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1". J. Biol. Chem. (UNITED STATES) 268 (6): 4259–66. PMID 8440710. 
22. ^ Finkel, T; Duc J, Fearon E R, Dang C V, Tomaselli G F (Jan. 1993). "Detection and modulation in vivo of helix-loop-helix protein-protein interactions". J. Biol. Chem. (UNITED STATES) 268 (1): 5–8. PMID 8380166. 
23. ^ Venugopal, R; Jaiswal A K (Dec. 1998). "Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes". Oncogene (ENGLAND) 17 (24): 3145–56. doi:10.1038/sj.onc.1202237. PMID 9872330. 
24. ^ Zhang, Y; Feng X H, Derynck R (Aug. 1998). "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription". Nature (ENGLAND) 394 (6696): 909–13. doi:10.1038/29814. PMID 9732876. 

Further reading

• Murphy LC, Alkhalaf M, Dotzlaw H, et al. (1994). "Regulation of gene expression in T-47D human breast cancer cells by progestins and antiprogestins". Hum. Reprod. 9 Suppl 1: 174–80. PMID 7962462. 
• Pompeiano M, Cirelli C, Arrighi P, Tononi G (1997). "c-Fos expression during wakefulness and sleep". Neurophysiologie clinique (Clinical neurophysiology) 25 (6): 329–41. doi:10.1016/0987-7053(96)84906-9. PMID 8904195. 
• Herrera DG, Robertson HA (1997). "Activation of c-fos in the brain". Prog. Neurobiol. 50 (2–3): 83–107. doi:10.1016/S0301-0082(96)00021-4. PMID 8971979. 
• Velazquez Torres A, Gariglio Vidal P (2002). "[Possible role of transcription factor AP1 in the tissue-specific regulation of human papillomavirus]" (in Spanish). Rev. Invest. Clin. 54 (3): 231–42. PMID 12183893. 

External links

• MeSH c-fos+Proteins
• MeSH c-fos+Genes
• FactorBook C-Fos
• Drosophila kayak - The Interactive Fly