View source for Biology:C-Fos

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{{Infobox_gene}}
In the fields of [[Biology:Molecular biology|molecular biology]] and [[Biology:Genetics|genetics]], '''c-Fos''' is a proto-oncogene that is the human homolog of the retroviral [[Biology:Oncogene|oncogene]] v-fos.<ref>Curran, T: The c-fos proto-oncogene. In: Reddy EP, Skalka AM, Curran T (eds.). The Oncogene Handbook 1988 Elsevier, New York, pp 307–327,</ref> It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkins murine osteogenic sarcoma virus) (Curran and Tech, 1982). It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2.<ref name="pmid16199154">{{cite journal | author = Milde-Langosch K | title = The Fos family of transcription factors and their role in tumourigenesis | journal = Eur. J. Cancer | volume = 41 | issue = 16 | pages = 2449–61 |date=November 2005 | pmid = 16199154 | doi = 10.1016/j.ejca.2005.08.008 }}</ref> It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun (part of Jun family of transcription factors), resulting in the formation of [[Biology:AP-1 transcription factor|AP-1]] (Activator Protein-1) complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression.<ref name="pmid3135940">{{cite journal | vauthors = Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M | title = The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes | journal = Cell | volume = 54 | issue = 4 | pages = 541–52 |date=August 1988 | pmid = 3135940 | doi = 10.1016/0092-8674(88)90076-1 | s2cid = 43078284 }}</ref> It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.

== Structure and function ==

c-Fos is a 380 amino acid protein with a basic [[Biology:Leucine zipper|leucine zipper]] region for dimerisation and DNA-binding and a transactivation domain at C-terminus, and, like Jun proteins, it can form homodimers.<ref name="pmid26303532">{{cite journal | vauthors = Szalóki N, Krieger JW, Komáromi I, Tóth K, Vámosi G | title = Evidence for homodimerization of the c-Fos transcription factor in live cells revealed by fluorescence microscopy and computer modeling |url= | journal = Mol. Cell. Biol. | volume = 35 | issue = 21 | pages = 3785–98 |date=November 2015 | pmid = 26303532 | pmc = 4589601 | doi = 10.1128/MCB.00346-15 }}</ref> ''In vitro'' studies have shown that Jun–Fos heterodimers are more stable and have stronger DNA-binding activity than Jun–Jun homodimers.<ref name="pmid3142692">{{cite journal | vauthors = Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P | title = c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities |url=http://genesdev.cshlp.org/content/2/12b/1687.full.pdf| journal = Cell | volume = 55 | issue = 5 | pages = 917–24 |date=December 1988 | pmid = 3142692 | doi = 10.1016/0092-8674(88)90147-X | s2cid = 19876513 }}</ref>

A variety of stimuli, including [[Biology:Serum (blood)|serum]], growth factors, tumor promoters, cytokines, and UV radiation induce their expression. The c-fos mRNA and protein is generally among the first to be expressed and hence referred to as an [[Biology:Immediate early gene|immediate early gene]]. It is rapidly and transiently induced, within 15 minutes of stimulation.<ref name="pmid8039503">{{cite journal | vauthors = Hu E, Mueller E, Oliviero S, Papaioannou VE, Johnson R, Spiegelman BM | title = Targeted disruption of the c-fos gene demonstrates c-fos-dependent and -independent pathways for gene expression stimulated by growth factors or oncogenes | journal = EMBO J. | volume = 13 | issue = 13 | pages = 3094–103 |date=July 1994 | pmid = 8039503 | pmc = 395200 | doi = 10.1002/j.1460-2075.1994.tb06608.x}}</ref> Its activity is also regulated by posttranslational modification caused by phosphorylation by different kinases, like MAPK, CDC2, PKA or PKC which influence protein stability, DNA-binding activity and the trans-activating potential of the transcription factors.<ref name="pmid8058317">{{cite journal | vauthors = Gruda MC, Kovary K, Metz R, Bravo R | title = Regulation of Fra-1 and Fra-2 phosphorylation differs during the cell cycle of fibroblasts and phosphorylation in vitro by MAP kinase affects DNA binding activity | journal = Oncogene | volume = 9 | issue = 9 | pages = 2537–47 |date=September 1994 | pmid = 8058317 }}</ref><ref name="pmid12197835">{{cite journal | vauthors = Hurd TW, Culbert AA, Webster KJ, Tavaré JM | title = Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent regulation of Fra-1 (fos-related antigen-1) transcription and phosphorylation | journal = Biochem. J. | volume = 368 | issue = Pt 2 | pages = 573–80 |date=December 2002 | pmid = 12197835 | pmc = 1223008 | doi = 10.1042/BJ20020579 }}</ref><ref name="pmid9873060">{{cite journal | vauthors = Rosenberger SF, Finch JS, Gupta A, Bowden GT | title = Extracellular signal-regulated kinase 1/2-mediated phosphorylation of JunD and FosB is required for okadaic acid-induced activator protein 1 activation | journal = J. Biol. Chem. | volume = 274 | issue = 2 | pages = 1124–30 |date=January 1999 | pmid = 9873060 | doi =10.1074/jbc.274.2.1124  | doi-access = free }}</ref> It can cause gene repression as well as gene activation, although different domains are believed to be involved in both processes.

It is involved in important cellular events, including cell proliferation, differentiation and survival; genes associated with [[Medicine:Hypoxia (medical)|hypoxia]]; and [[Biology:Angiogenesis|angiogenesis]];<ref name="pmid10963134">{{cite journal | author = Tulchinsky E | title = Fos family members: regulation, structure and role in oncogenic transformation | journal = Histol. Histopathol. | volume = 15 | issue = 3 | pages = 921–8 |date=July 2000 | pmid = 10963134 }}</ref> which makes its dysregulation an important factor for cancer development. It can also induce a loss of cell polarity and epithelial-mesenchymal transition, leading to invasive and metastatic growth in mammary epithelial cells.<ref name="pmid8601589">{{cite journal | vauthors = Fialka I, Schwarz H, Reichmann E, Oft M, Busslinger M, Beug H | title = The estrogen-dependent c-JunER protein causes a reversible loss of mammary epithelial cell polarity involving a destabilization of adherens junctions | journal = J. Cell Biol. | volume = 132 | issue = 6 | pages = 1115–32 |date=March 1996 | pmid = 8601589 | pmc = 2120757 | doi =10.1083/jcb.132.6.1115 }}</ref>

The importance of c-fos in biological context has been determined by eliminating endogenous function by using anti-sense mRNA, anti-c-fos antibodies, a [[Biology:Ribozyme|ribozyme]] that cleaves c-fos mRNA or a dominant negative mutant of c-fos. The transgenic mice thus generated are viable, demonstrating that there are c-fos dependent and independent pathways of cell proliferation,  but display a range of tissue-specific developmental defects, including [[Medicine:Osteoporosis|osteoporosis]], delayed [[Biology:Gametogenesis|gametogenesis]], lymphopenia and behavioral abnormalities.

== Clinical significance ==
{{psychostimulant addiction|align=right}}
The AP-1 complex has been implicated in [[Biology:Transformation (genetics)|transformation]] and progression of [[Medicine:Cancer|cancer]]. In [[Medicine:Osteosarcoma|osteosarcoma]] and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and poor prognosis. Also, in a comparison between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was significantly lower in precancerous lesions. c-Fos has also been identified as independent predictor of decreased survival in [[Medicine:Breast cancer|breast cancer]].<ref name="pmid18854825">{{cite journal | vauthors = Mahner S, Baasch C, Schwarz J, Hein S, Wölber L, Jänicke F, Milde-Langosch K | title = C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma | journal = Br. J. Cancer | volume = 99 | issue = 8 | pages = 1269–75 |date=October 2008 | pmid = 18854825 | pmc = 2570515 | doi = 10.1038/sj.bjc.6604650 }}</ref>

It was found that overexpression of c-fos from class I MHC promoter in transgenic mice leads to the formation of osteosarcomas due to increased proliferation of osteoblasts whereas ectopic expression of the other Jun and Fos proteins does not induce any malignant tumors.  Activation of the c-Fos  transgene in mice results in overexpression of cyclin D1, A and E in osteoblasts and chondrocytes, both ''in vitro'' and ''in vivo'', which might contribute to the uncontrolled growth leading to tumor. Human osteosarcomas analyzed for c-fos expression have given positive results in more than half the cases and c-fos expression has been associated with higher frequency of relapse and poor response to chemotherapy.

Several studies have raised the idea that c-Fos may also have tumor-suppressor activity, that it might be able to promote as well as suppress tumorigenesis.  Supporting this is the observation that in ovarian carcinomas, loss of c-Fos expression correlates with disease progression. This double action could be enabled by differential protein composition of tumour cells and their environment, for example, dimerisation partners, co-activators and promoter architecture.  It is possible that the tumor suppressing activity is due to a proapoptotic function. The exact mechanism by which c-Fos contributes to [[Biology:Apoptosis|apoptosis]] is not clearly understood, but observations in human hepatocellular carcinoma cells indicate that c-Fos is a mediator of c-myc-induced cell death and might induce apoptosis through the p38 MAP kinase pathway. Fas ligand (FASLG or FasL) and the tumour necrosis factor-related apoptosis-inducing ligand (TNFSF10 or TRAIL) might reflect an additional apoptotic mechanism induced by c-Fos, as observed in a human T-cell leukaemia cell line. Another possible mechanism of c-Fos involvement in tumour suppression could be the direct regulation of BRCA1, a well established factor in familial breast and ovarian cancer.

In addition, the role of c-fos and other Fos family proteins has also been studied in endometrial carcinoma, cervical cancer, mesotheliomas, colorectal cancer, lung cancer, melanomas, thyroid carcinomas, esophageal cancer, hepatocellular carcinomas, etc.

Cocaine, methamphetamine,<ref name="pmid2118661">{{cite journal | vauthors = Graybiel AM, Moratalla R, Robertson HA | title = Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 87 | issue = 17 | pages = 6912–6 |date=September 1990 | pmid = 2118661 | pmc = 54648 | doi =10.1073/pnas.87.17.6912 | bibcode = 1990PNAS...87.6912G | doi-access = free }}</ref> morphine,<ref name="pmid8947933">{{cite journal | vauthors = Curran EJ, Akil H, Watson SJ | title = Psychomotor stimulant- and opiate-induced c-fos mRNA expression patterns in the rat forebrain: comparisons between acute drug treatment and a drug challenge in sensitized animals | journal = Neurochem. Res. | volume = 21 | issue = 11 | pages = 1425–35 |date=November 1996 | pmid = 8947933 | doi =10.1007/BF02532384  | s2cid = 6727581 }}</ref> and other psychoactive drugs<ref name="pmid11927188">{{cite journal | vauthors = Nichols CD, Sanders-Bush E | title = A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain | journal = Neuropsychopharmacology | volume = 26 | issue = 5 | pages = 634–42 |date=May 2002 | pmid = 11927188 | doi = 10.1016/S0893-133X(01)00405-5 | doi-access = free }}</ref><ref name="pmid12586446">{{cite journal | vauthors = Singewald N, Salchner P, Sharp T | title = Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs | journal = Biol. Psychiatry | volume = 53 | issue = 4 | pages = 275–83 |date=February 2003 | pmid = 12586446 | doi =10.1016/S0006-3223(02)01574-3 | s2cid = 29821546 }}</ref> have been shown to increase c-Fos production in the [[Chemistry:Mesocortical pathway|mesocortical pathway]] (prefrontal cortex) as well as in the mesolimbic reward pathway (nucleus accumbens), as well as display variability depending on prior sensitization.<ref name="pmid12586446" /> c-Fos repression by [[Biology:ΔFosB|ΔFosB]]'s [[Biology:AP-1 transcription factor|AP-1 complex]] within the D1-type [[Biology:Medium spiny neuron|medium spiny neuron]]s of the [[Biology:Nucleus accumbens|nucleus accumbens]] acts as a molecular switch that enables the chronic induction of ΔFosB, thus allowing it to accumulate more rapidly. As such, the c-Fos promoter finds utilization in drug addiction research in general, as well as with context-induced relapse to drug-seeking and other behavioral changes associated with chronic drug taking.

An increase in c-Fos production in androgen receptor-containing neurons has been observed in rats after mating.

== Applications ==

Expression of c-fos is an indirect marker of neuronal activity because c-fos is often expressed when neurons fire action potentials.<ref name="pmid19050162">{{cite journal | vauthors = VanElzakker M, Fevurly RD, Breindel T, Spencer RL | title = Environmental novelty is associated with a selective increase in c-fos expression in the output elements of the hippocampal formation and the perirhinal cortex | journal = Learn. Mem. | volume = 15 | issue = 12 | pages = 899–908 | year = 2008 | pmid = 19050162 | doi = 10.1101/lm.1196508 | pmc = 2632843 }}</ref><ref name="pmid2507830">{{cite journal | vauthors = Dragunow M, Faull R | title = The use of c-fos as a metabolic marker in neuronal pathway tracing | journal = Journal of Neuroscience Methods | volume = 29 | issue = 3 | pages = 261–265 | year = 1989 | pmid = 2507830 | doi = 10.1016/0165-0270(89)90150-7 | s2cid = 3804201 }}</ref> Upregulation of c-fos mRNA in a neuron indicates recent activity.<ref name="pmid18634767">{{cite journal | vauthors = Day HE, Kryskow EM, Nyhuis TJ, Herlihy L, Campeau S | title = Conditioned Fear Inhibits c-fos mRNA Expression in the Central Extended Amygdala | journal = Brain Res. | volume = 1229 | pages = 137–46 |date=September 2008 | pmid = 18634767 | pmc = 2605076 | doi = 10.1016/j.brainres.2008.06.085 }}</ref>

The c-fos promoter has also been utilised for drug abuse research. Scientists use this promoter to turn on transgenes in rats, allowing them to manipulate specific neuronal ensembles to assess their role in drug-related memories and behavior.<ref name="pmid19620976">{{cite journal | vauthors = Koya E, Golden SA, Harvey BK, Guez-Barber DH, Berkow A, Simmons DE, Bossert JM, Nair SG, Uejima JL, Marin MT, Mitchell TB, Farquhar D, Ghosh SC, Mattson BJ, Hope BT | title = Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization | journal = Nat. Neurosci. | volume = 12 | issue = 8 | pages = 1069–73 |date=August 2009 | pmid = 19620976 | pmc = 2752202 | doi = 10.1038/nn.2364  }}</ref> This neuronal control can be replicated with [[Optogenetics|optogenetics]] or DREADDs <ref>{{cite journal|last1=Garner|first1=Aleena|title=Generation of a Synthetic Memory Trace|journal=Science|date=March 2012|volume=335|issue=6075|pages=1513–1516|doi=10.1126/science.1214985|pmid=22442487|pmc=3956300|bibcode=2012Sci...335.1513G}}<!--|access-date=7 December 2014--></ref>

== Interactions ==

c-Fos has been shown to interact with:
* [[Biology:BCL3|BCL3]],<ref name="pmid10497212">{{cite journal | vauthors = Na SY, Choi JE, Kim HJ, Jhun BH, Lee YC, Lee JW | title = Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation | journal = J. Biol. Chem. | volume = 274 | issue = 40 | pages = 28491–6 |date=October 1999 | pmid = 10497212 | doi = 10.1074/jbc.274.40.28491 | doi-access = free }}</ref>
* COBRA1,<ref name="pmid15530430">{{cite journal | vauthors = Zhong H, Zhu J, Zhang H, Ding L, Sun Y, Huang C, Ye Q | title = COBRA1 inhibits AP-1 transcriptional activity in transfected cells | journal = Biochem. Biophys. Res. Commun. | volume = 325 | issue = 2 | pages = 568–73 |date=December 2004 | pmid = 15530430 | doi = 10.1016/j.bbrc.2004.10.079 }}</ref>
* CSNK2A1,<ref name=pmid9685505/> 
* CSNK2A2,<ref name="pmid9685505">{{cite journal | vauthors = Yamaguchi Y, Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H | title = Casein kinase II interacts with the bZIP domains of several transcription factors | journal = Nucleic Acids Res. | volume = 26 | issue = 16 | pages = 3854–61 |date=August 1998 | pmid = 9685505 | pmc = 147779 | doi = 10.1093/nar/26.16.3854 }}</ref> 
* [[Biology:DNA damage-inducible transcript 3|DDIT3]],<ref name="pmid10523647">{{cite journal | vauthors = Ubeda M, Vallejo M, Habener JF | title = CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins | journal = Mol. Cell. Biol. | volume = 19 | issue = 11 | pages = 7589–99 |date=November 1999 | pmid = 10523647 | pmc = 84780 | doi = 10.1128/MCB.19.11.7589}}</ref>
* JUN<ref name=pmid10488148/><ref name="pmid11053448">{{cite journal | vauthors = Ito T, Yamauchi M, Nishina M, Yamamichi N, Mizutani T, Ui M, Murakami M, Iba H | title = Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers | journal = J. Biol. Chem. | volume = 276 | issue = 4 | pages = 2852–7 |date=January 2001 | pmid = 11053448 | doi = 10.1074/jbc.M009633200  | doi-access = free }}</ref><ref name="pmid9160889">{{cite journal | vauthors = Pognonec P, Boulukos KE, Aperlo C, Fujimoto M, Ariga H, Nomoto A, Kato H | title = Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity | journal = Oncogene | volume = 14 | issue = 17 | pages = 2091–8 |date=May 1997 | pmid = 9160889 | doi = 10.1038/sj.onc.1201046 | doi-access = free }}</ref><ref name="pmid7816143">{{cite journal | vauthors = Glover JN, Harrison SC | title = Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA | journal = Nature | volume = 373 | issue = 6511 | pages = 257–61 |date=January 1995 | pmid = 7816143 | doi = 10.1038/373257a0 | bibcode = 1995Natur.373..257G | s2cid = 4276971 }}</ref><ref name="pmid8440710">{{cite journal | vauthors = Nomura N, Zu YL, Maekawa T, Tabata S, Akiyama T, Ishii S | title = Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1 | journal = J. Biol. Chem. | volume = 268 | issue = 6 | pages = 4259–66 |date=February 1993 | doi = 10.1016/S0021-9258(18)53604-8 | pmid = 8440710 | doi-access = free }}</ref><ref name="pmid8380166">{{cite journal | vauthors = Finkel T, Duc J, Fearon ER, Dang CV, Tomaselli GF | title = Detection and modulation in vivo of helix-loop-helix protein-protein interactions | journal = J. Biol. Chem. | volume = 268 | issue = 1 | pages = 5–8 |date=January 1993 | doi = 10.1016/S0021-9258(18)54105-3 | pmid = 8380166 | doi-access = free }}</ref><ref name="pmid9872330">{{cite journal | vauthors = Venugopal R, Jaiswal AK | title = Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes | journal = Oncogene | volume = 17 | issue = 24 | pages = 3145–56 |date=December 1998 | pmid = 9872330 | doi = 10.1038/sj.onc.1202237 | doi-access = free }}</ref>
* [[Biology:Nuclear receptor coactivator 1|NCOA1]];,<ref name="pmid10847592">{{cite journal | vauthors = Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW | title = Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2 | journal = Mol. Endocrinol. | volume = 14 | issue = 6 | pages = 915–25 |date=June 2000 | pmid = 10847592 | doi = 10.1210/mend.14.6.0471 | doi-access = free }}</ref><ref name="pmid9642216">{{cite journal | vauthors = Lee SK, Kim HJ, Na SY, Kim TS, Choi HS, Im SY, Lee JW | title = Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits | journal = J. Biol. Chem. | volume = 273 | issue = 27 | pages = 16651–4 |date=July 1998 | pmid = 9642216 | doi = 10.1074/jbc.273.27.16651 | doi-access = free }}</ref>
* [[Biology:Nuclear receptor co-repressor 2|NCOR2]],<ref name="pmid10777532">{{cite journal | vauthors = Lee SK, Kim JH, Lee YC, Cheong J, Lee JW | title = 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 | journal = J. Biol. Chem. | volume = 275 | issue = 17 | pages = 12470–4 |date=April 2000 | pmid = 10777532 | doi = 10.1074/jbc.275.17.12470 | doi-access = free }}</ref>
* [[Biology:RELA|RELA]],<ref name="pmid10488148">{{cite journal | vauthors = Yang X, Chen Y, Gabuzda D | title = ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-kappaB | journal = J. Biol. Chem. | volume = 274 | issue = 39 | pages = 27981–8 |date=September 1999 | pmid = 10488148 | doi = 10.1074/jbc.274.39.27981 | doi-access = free }}</ref>
* [[Biology:RUNX1|RUNX1]],<ref name=pmid11274169/><ref name=pmid11641401/> 
* [[Biology:RUNX2|RUNX2]],<ref name="pmid11274169">{{cite journal | vauthors = Hess J, Porte D, Munz C, Angel P | title = 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 | journal = J. Biol. Chem. | volume = 276 | issue = 23 | pages = 20029–38 |date=June 2001 | pmid = 11274169 | doi = 10.1074/jbc.M010601200 | doi-access = free }}</ref><ref name="pmid11641401">{{cite journal | vauthors = D'Alonzo RC, Selvamurugan N, Karsenty G, Partridge NC | title = Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation | journal = J. Biol. Chem. | volume = 277 | issue = 1 | pages = 816–22 |date=January 2002 | pmid = 11641401 | doi = 10.1074/jbc.M107082200 | doi-access = free }}</ref>
* [[Biology:Mothers against decapentaplegic homolog 3|SMAD3]],<ref name="pmid9732876">{{cite journal | vauthors = Zhang Y, Feng XH, Derynck R | title = Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription | journal = Nature | volume = 394 | issue = 6696 | pages = 909–13 |date=August 1998 | pmid = 9732876 | doi = 10.1038/29814  | bibcode = 1998Natur.394..909Z | s2cid = 4393852 }}</ref> and
* TBP.<ref name="pmid8065335">{{cite journal | vauthors = Metz R, Bannister AJ, Sutherland JA, Hagemeier C, O'Rourke EC, Cook A, Bravo R, Kouzarides T | title = c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein | journal = Mol. Cell. Biol. | volume = 14 | issue = 9 | pages = 6021–9 |date=September 1994 | pmid = 8065335 | pmc = 359128 | doi =10.1128/MCB.14.9.6021  }}</ref>

{|
|[[Image:Signal transduction pathways.svg|500px|Overview of signal transduction pathways involved in apoptosis.]]
|}

[[File:CFos-expression-in-stimulated-neurons.jpg|500px|thumb|Mixed neural cultures derived from rat embryos were grown under normal conditions (left) or treated with 55mM Potassium for 5 hours (right). Cultures were then stained with antibody to the [[Biology:Intermediate filament|intermediate filament]] protein vimentin (green), antibody to cFos (red) and with a DNA binding dye (blue). The vimentin antibody reveals non-neuronal cells and the DNA dye shows the nuclei of all cells. The potassium treatment depolarizes the neurons and induces strong expression of cFos in neuronal cell bodies as shown in the right image. Cell culture, Image and antibody generation all performed in the EnCor Biotechnology laboratory.]]

==See also==
*[[Chemistry:Leptomycin|Leptomycin]]
*c-Jun
*Egr-1

==References==
{{Reflist|35em}}
{{reflist|group=Color legend}}

==Further reading==
{{refbegin|35em}}
* {{cite journal | vauthors = Murphy LC, Alkhalaf M, Dotzlaw H, Coutts A, Haddad-Alkhalaf B | title = Regulation of gene expression in T-47D human breast cancer cells by progestins and antiprogestins | journal = Hum. Reprod. | volume = 9 Suppl 1 | pages = 174–80 |date=June 1994 | pmid = 7962462 | doi =10.1093/humrep/9.suppl_1.174 }}
* {{cite journal | vauthors = Pompeiano M, Cirelli C, Arrighi P, Tononi G | title = c-Fos expression during wakefulness and sleep | journal = Neurophysiol Clin | volume = 25 | issue = 6 | pages = 329–41 | year = 1995 | pmid = 8904195 | doi = 10.1016/0987-7053(96)84906-9 | s2cid = 23760149 }}
* {{cite journal | vauthors = Herrera DG, Robertson HA | title = Activation of c-fos in the brain | journal = Prog. Neurobiol. | volume = 50 | issue = 2–3 | pages = 83–107 |date=October 1996 | pmid = 8971979 | doi = 10.1016/S0301-0082(96)00021-4  | s2cid = 31105978 }}
* {{cite journal | vauthors = Velazquez Torres A, Gariglio Vidal P | title = [Possible role of transcription factor AP1 in the tissue-specific regulation of human papillomavirus] | language = es| journal = Rev. Invest. Clin. | volume = 54 | issue = 3 | pages = 231–42 | year = 2002 | pmid = 12183893 }}
{{refend}}

==External links==
*{{MeshName|c-fos+Proteins}}
*{{MeshName|c-fos+Genes}}
*{{FactorBook|c-Fos}}
*[http://www.sdbonline.org/fly/gene/fos1.htm ''Drosophila'' ''kayak'' - The Interactive Fly]
* {{UCSC gene info|FOS}}
* {{PDBe-KB2|P01100|Human Proto-oncogene c-Fos}}
* {{PDBe-KB2|P01101|Mouse Proto-oncogene c-Fos}}

{{PDB Gallery|geneid=2353}}
{{Oncogenes}}
{{Transcription factors|g1}}

[[Category:Oncogenes]]
[[Category:Transcription factors]]

{{Sourceattribution|C-Fos|1}}