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FOSL1 (FOS-like antigen 1)

Written2012-11Senthilkumar B Rajamohan, Sekhar P Reddy
Department of Medicine, Institute for Integrative Physiology, University of Chicago, Chicago, Illinois, USA (SBR); Department of Pediatrics, University of Illinois, Chicago, Illinois, USA (SPR)

(Note : for Links provided by Atlas : click)


HGNC Alias symbfra-1
HGNC Previous nameFOS like antigen 1
LocusID (NCBI) 8061
Atlas_Id 40622
Location 11q13.1  [Link to chromosome band 11q13]
Location_base_pair Starts at 65892049 and ends at 65900388 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping FOSL1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
FOSL1 (11q13.1)::GIT1 (17q11.2)


  Transcriptional regulation of Fra-1 (Fosl-1): MAPK signaling activates transcriptional factors binding at the human Fra-1 promoter. Binding of Fra-1 and c-Jun to TRE sites of first intron regulates Fra-1 transcription. TRE - TPA response element, SRE - Serum response element, SRF - serum response factor, ATF - activating transcription factor binding site
Description Fra-1 (Fosl-1) is a basic leucine zipper (bZIP) transcription factor and a member of Fos family of proteins (Cohen and Curran, 1988). The Fra-1 gene spans about 8.31 kb including four exons and is located on chromosome 11q13. It contains two regulatory elements, an upstream 5'-flanking region and an intragenic sequence, that are known to regulate its transcriptional induction (Verde et al., 2007). Two critical elements of the promoter, the upstream TPA response element (TRE) and the serum response element (SRE), are required for Fra-1 transcriptional induction in response to external stimuli, such as mitogens and cytokines (Adiseshaiah et al., 2003; Adiseshaiah et al., 2005). The intragenic regulatory element containing the TRE/TRE-like elements also contribute to Fra-1 induction (Bergers et al., 2005).
Transcription Fra-1 transcription is strongly inducible by mitogens and inflammatory cytokines as well by a wide variety of environmental toxicants, carcinogens, and pathogens. In contrast to the early activation of c-Jun and c-Fos (which peaks at 15-30 min), the induction of Fra-1 by various mitogenic and stressful stimuli peaks at 90-180 min, and this delayed induction is postulated to play important role in modulating the transcriptional response initiated by the AP-1 complex composed of Jun/c-Fos dimers. The Fra-1 promoter region contains a c-Fos-like serum response element (SRE), which is constitutively occupied by the serum response factor (SRF) and the ternary complex factor, Elk1. Recruitment of c-Jun to the upstream TRE and the presence of downstream SRE as well as the activating transcription factor (ATF) site are essential for Fra-1 induction by mitogenic and cytokine stimuli (Adiseshaiah et al., 2007). Sp1 family members also regulate Fra-1 transcription (Adiseshaiah et al., 2005). Other studies have shown that cis-elements, such as TRE and E boxes, located in the intragenic region also contribute to Fra-1 transcription (Bergers et al., 1995, Casalino et al., 2003,). Histone modifications, such as the phosphorylation of Histone 3 by PIM1 on the nucleasome at the MYC binding sites, regulate the transcriptional activation of Fra-1 (Zippo et al., 2007). In addition to transcriptional induction, ERK- dependent phosphorylation has been shown to play a key role in the protein stability and DNA binding activity of Fra-1 (Basbous et al., 2007, Young et al., 2002).
Pseudogene One pseudo gene is identified, the FOS-like antigen pseudogene, FOSL1P1 (NCBI, HGNC ID: 44055).


  A schematic diagram showing the modular structure of Fra-1 (1-271 AA). DBD -DNA binding domain, LZD - leucine-zipper domain, N - amino terminus, C - carboxyl terminus. P1 - Thr 231, P2 - Ser252, P3 - Ser265. In this, ERK mediated phosphorylation of serine residues 252 and 265 requires for the stabilization of Fra-1 in certain tumor cell lines (Basbous et al., 2007).
Description Fra-1 (Fosl-1) protein encodes for 271 amino acids with an expected molecular weight of 29.4 kDa. However, in immunoblot analysis of cellular extracts isolated from cells stimulated with growth factors or from cancer cells, Fra-1 exhibits multiple forms ranging from 30-40 kDa. The appearance of these multiple forms is mainly attributed to post-translational modification (e.g., phosphorylation) of this protein. Human and mouse Fra-1 exhibits 6 and 1 splice variants, respectively, and both exhibit one unspliced form. These different transcripts encode proteins with different functional domains. The functional significance of these alternatively spliced variants of Fra-1 for both in physiology and pathological processes remains unclear.
Expression The expression of Fra-1 is high in smooth muscle cells, bronchial epithelial cells (trachea), and the pancreas, but its expression is low in other tissues, such as the brain and prostate.
Localisation Fra-1 (Fosl-1) contains a nuclear localization signal and is predominantly found in the nucleus. However, Fra-1 antigen is observed in the cytoplasm under certain conditions, such as elevated levels of oxidative stress (Burch et al., 2004) and in cancerous tissues (Song et al., 2006). Furthermore, a distinct cytoplasmic location of Fra-1 has been noted in non-small-cell lung cancer (Ma et al., 2009). Nuclear and cytoplasmic expression of Fra-1 is markedly elevated in human adenomas, adenocarcinomas and neuroendocrine carcinomas (Zhang et al., 2005).
Function After dimerization, mainly with the Jun or ATF family of proteins, Fra-1 binds to the TPA response element (TRE, or AP-1 site) and regulates gene expression in a context-dependent manner (Cohen et al., 1989). Fra-1 plays important roles in various biological processes, including inflammation, transformation, proliferation, and metastasis. Increased expression levels of Fra-1 is detectable in breast, lung, brain, colon and prostate cancers and its knockdown affects cancer cell progression (see below).
Homology The Fra-1 gene is conserved in chimpanzee, dog, cow, mouse, rat, and Zebra fish.


Note No genetic mutations leading to activation or inactivation of this transcription factor in human disease development and in malignancies have been yet documented. Recently, the presence of SNPs was demonstrated in human Fra-1 (FOSL-1) gene, and these SNPs were shown to be associated with a decreased rate of lung function (Sandford et al., 2012).

Implicated in

Entity Thyroid cancer
Note Analysis of samples from thyroid cancer patients has shown an increase in Fra-1 protein expression in thyroid nodules (Chiappetta et al., 2000). Induction of Fra-1 expression has also been observed in human thyroid cancer cell lines (Battista et al., 1998). Inhibition of Fra-1 prevents the retrovirally induced neoplastic transformation of rat thyroid cells (Vallone et al., 1997). In thyroid cancer cells, Fra-1 binds to the cyclin A promoter and regulates its expression during cell-cycle progression (Casalino et al., 2007).
Entity Non-small-cell lung cancer (NSCLC)
Note Expression of AP-1 family proteins, and particularly Fra-1 has been detected in NSCLC cell lines (Risse-Hackl et al., 1998). Decreased levels of Fra-1 protein expression have been noted in the tumor tissue of non small cell lung cancer patients (Ma et al., 2009), and these decreased levels have been positively correlated with progression of tumor stage and worsening prognosis. Ectopic expression of Fra-1 in lung adenocarcinoma cells induces cancer. Interestingly, it has been reported that a DNA vaccine specific to Fra-1 prevents pulmonary cancer metastasis in syngeneic mice (Luo et al., 2005).
Entity Breast cancer
Note Increased expression of Fra-1 was observed in human breast cancer cells (Philips et al., 1998). Several studies have shown its involvement in cancer cell proliferation, motility and invasiveness (Bamberger et al., 1999; Belguise et al., 2005; Logullo et al., 2011). An increase in nuclear or cytoplasmic localization of Fra-1 has been considered as a marker of progression of breast cancer (Song et al., 2006, Chiappetta et al., 2007). Knockdown of Fra-1 in tumor associated macrophages with small interfering RNA has been found to significantly suppress the invasion, angiogenesis and metastasis of breast cancer tumor cells (Luo et al., 2010). Likewise, knockdown of Fra-1 in estrogen- resistant MCF-7 cells significantly affected their growth and enhanced their susceptibility to cell death in response to estrogen treatment (Pennanen et al., 2011). An increased accumulation of Fra-1 protein in estrogen-negative breast cancer cells is mediated through PKCθ pathway (Belguise et al., 2012). A mouse Fra-1 targeted DNA vaccine has been found to be effective in protection against breast cancer in mice (Luo et al., 2003). Low level of miRNA-34 has been correlated with an elevated level of Fra-1 expression in breast cancer tissues and cell lines, but ectopic miRNA-34 expression causes a down-regulation of Fra-1 levels and inhibits breast cancer cell progression (Yang et al., 2012). In a different study, Fra-1 overexpression was shown to increase the chemosensitive of breast cancer stem cells, suggesting Fra-1 can be considered as a prognostic responsive marker in breast cancer therapy (Lu et al., 2012).
Entity Bladder cancer
Note An increased level of Fra-1 expression is found in bladder tumor and cancer cell lines. Fra-1, via the transcriptional induction of the receptor tyrosine kinase AXL, promotes bladder cancer cell motility (Sayan et al., 2012).
Entity Colon cancer
Note Fra-1 and its dimeric partner, c-Jun, are up-regulated in human colorectal tumors (Zhang et al., 2005; Wang et al., 2002). In colon carcinoma cells, the basal induction and stabilization of Fra-1 has been shown to be regulated by ERK activity, and knockdown of Fra-1 suppresses colon cancer cell polarization and progression (Vial and Marshall, 2003). A potential role for Fra-1 in the regulation of vimentin during Ha-RAS-induced epithelial-to- mesenchymal transition and migration has been documented (Andreolas et al., 2008). By upregulating miR-34a, p53 indirectly down regulates Fra-1 mRNA and protein expression in colon cancer cells and inhibits cell migration and invasion (Wu et al., 2012).
Entity Prostate cancer
Note Akt signaling contributes to Fra-1 induction in the prostate cancer cells, mainly at the transcription level (Tiwari et al., 2003). An abnormal activation of Fra-1 has been linked to elevated expression levels of IL-6, which promote prostate cancer cell progression and resistance to chemotherapeutic agents (Zerbini et al., 2003).
Entity Esophageal squamous cell carcinoma (ESCC)
Note Immunoreactive analysis of two different ESCC cell lines (HKESC-1 and HKESC-2) derived from ESCC patients has demonstrated Fra-1 expression in these cell line (Hu et al., 2001). An elevated level of Fra-1expression is associated with poor prognosis of ESCC. Furthermore, Fra-1 knockdown in ESCC cell lines decreases tumor cell progression and invasion (Usui et al., 2012).
Entity Nasopharyngeal carcinoma (NPC)
Note Expression profiling of nasopharyngeal carcinoma and normal cells has revealed elevated expression levels of Fra-1 in NPC cancer cells (Fung et al., 2000). Fra-1 has been shown to play an important role in controlling latent membrane protein 2A (LMP2A)-induced NPC epithelial cell motility and invasiveness (Lan et al., 2012). Either inhibition of Fra-1 induction or suppression of ERK1 and ERK2 activation will block the LMP2A-induced MMP-9 expression required for cancer cell progression.
Entity Glioma
Note Ectopic Fra-1 expression in malignant glioma cells leads to phenotypic changes associated with invasiveness and tumorigenicity (Debinski and Gibo, 2005). In contrast, knock down of Fra-1 in high-grade glioma (HGG) cells alters the morphology, reduces both anchorage-independence and tumorigenic potential (Debinski and Gibo, 2011). In rat C6 glioma cells, Fra-1 overexpression suppresses their proliferation rate and tumorogenic potential and promotes cellular apoptosis (Shirsat and Shaikh., 2003).
Entity Head and neck squamous cell carcinoma (HNSCC)
Note Analysis of the tumor samples from patients with head and neck squamous cell carcinomas (HNSCC) has shown an increase in Fra-1 mRNA expression when compared to matched adjacent mucosa samples. Furthermore, tumor tissue staining for Fra-1 in tumor tissues is intensely more reactive immunoreactive than that of adjacent normal tissue (Mangone et al., 2005).
Entity Fibrosis
Note Fra-1 transgenic mice have been shown to be prone to developing biliary hepatic fibrosis, and Fra-1 has been associated with ductular proliferation and infiltration of inflammatory cells (Kireva et al., 2011). On the other hand, it negatively regulates pulmonary fibrosis (Rajasekaran et al., 2012). Genetic disruption of Fra-1 causes increased levels of inflammation, collagen accumulation, and profibrotic and fibrotic gene expression following bleomycin treatment when compared to wild-type Fra-1.
Entity Osteopetrosis
Note Genetic disruption of Fos leads to osteopetrosis in mice (Matsuo et al., 2000). However, over expression of Fra-1 rescues this phenotype in c-Fos mutant mice. Rankl, an osteoclast differentiation factor, has been reported to induce Fra-1 expression in a c-Fos-dependent manner, suggesting the involvement of c-Fos-RANKL-Fra-1 signaling in osteoclast differentiation. It has also been reported that overexpression of Fra-1 in mice increases bone mass up to 5-fold compared to wild-type mice (Roschger et al., 2004).
Entity Acute lung injury and Sepsis
Note Increased expression of Fra-1 has been reported in lung epithelial cell of acute respiratory syndrome patients (Fudala et al., 2011). Mice lacking Fra-1 show decreased levels of acute lung injury and inflammation as well as increased survival following endotoxin (LPS) treatment when compared to their wild-type counterparts (Vaz et al., 2012); this improvement was associated with diminished and increased levels of NF-kB and c-Jun/AP-1 binding, respectively. In agreement with this result, mice overexpressing Fra-1 were shown in another study to have enhanced susceptibility to endotoxin-induced death (Takada et al., 2011).


FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo.
Adiseshaiah P, Lindner DJ, Kalvakolanu DV, Reddy SP.
Cancer Res. 2007 Jul 1;67(13):6204-11.
PMID 17616677
Fra-1 regulates vimentin during Ha-RAS-induced epithelial mesenchymal transition in human colon carcinoma cells.
Andreolas C, Kalogeropoulou M, Voulgari A, Pintzas A.
Int J Cancer. 2008 Apr 15;122(8):1745-56.
PMID 18098284
Expression pattern of the AP-1 family in breast cancer: association of fosB expression with a well-differentiated, receptor-positive tumor phenotype.
Bamberger AM, Methner C, Lisboa BW, Stadtler C, Schulte HM, Loning T, Milde-Langosch K.
Int J Cancer. 1999 Oct 22;84(5):533-8.
PMID 10502734
Ubiquitin-independent proteasomal degradation of Fra-1 is antagonized by Erk1/2 pathway-mediated phosphorylation of a unique C-terminal destabilizer.
Basbous J, Chalbos D, Hipskind R, Jariel-Encontre I, Piechaczyk M.
Mol Cell Biol. 2007 Jun;27(11):3936-50. Epub 2007 Mar 19.
PMID 17371847
Increase in AP-1 activity is a general event in thyroid cell transformation in vitro and in vivo.
Battista S, de Nigris F, Fedele M, Chiappetta G, Scala S, Vallone D, Pierantoni GM, Mega T, Santoro M, Viglietto G, Verde P, Fusco A.
Oncogene. 1998 Jul 23;17(3):377-85.
PMID 9690519
The PKCθ pathway participates in the aberrant accumulation of Fra-1 protein in invasive ER-negative breast cancer cells.
Belguise K, Milord S, Galtier F, Moquet-Torcy G, Piechaczyk M, Chalbos D.
Oncogene. 2012 Nov 22;31(47):4889-97. doi: 10.1038/onc.2011.659. Epub 2012 Jan 30.
PMID 22286759
Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron.
Bergers G, Graninger P, Braselmann S, Wrighton C, Busslinger M.
Mol Cell Biol. 1995 Jul;15(7):3748-58.
PMID 7791782
An extracellular signal-regulated kinase 1- and 2-dependent program of chromatin trafficking of c-Fos and Fra-1 is required for cyclin D1 expression during cell cycle reentry.
Burch PM, Yuan Z, Loonen A, Heintz NH.
Mol Cell Biol. 2004 Jun;24(11):4696-709.
PMID 15143165
Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription.
Casalino L, Bakiri L, Talotta F, Weitzman JB, Fusco A, Yaniv M, Verde P.
EMBO J. 2007 Apr 4;26(7):1878-90. Epub 2007 Mar 8.
PMID 17347653
FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders.
Chiappetta G, Ferraro A, Botti G, Monaco M, Pasquinelli R, Vuttariello E, Arnaldi L, Di Bonito M, D'Aiuto G, Pierantoni GM, Fusco A.
BMC Cancer. 2007 Jan 25;7:17.
PMID 17254320
fra-1: a serum-inducible, cellular immediate-early gene that encodes a fos-related antigen.
Cohen DR, Curran T.
Mol Cell Biol. 1988 May;8(5):2063-9.
PMID 3133553
The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: transcription factor AP-1 is comprised of multiple protein complexes.
Cohen DR, Ferreira PC, Gentz R, Franza BR Jr, Curran T.
Genes Dev. 1989 Feb;3(2):173-84.
PMID 2497053
Fos-related antigen 1 (Fra-1) pairing with and transactivation of JunB in GBM cells.
Debinski W, Gibo DM.
Cancer Biol Ther. 2011 Jan 15;11(2):254-62. Epub 2011 Jan 15.
PMID 21088499
Increased levels of nuclear factor κB and Fos-related antigen 1 in lung tissues from patients with acute respiratory distress syndrome.
Fudala R, Allen TC, Krupa A, Cagle PT, Nash S, Gryczynski Z, Gryczynski I, Kurdowska AK.
Arch Pathol Lab Med. 2011 May;135(5):647-54. doi: 10.1043/2009-0660-OAR1.1.
PMID 21526963
Differential gene expression in nasopharyngeal carcinoma cells.
Fung LF, Lo AK, Yuen PW, Liu Y, Wang XH, Tsao SW.
Life Sci. 2000 Jul 14;67(8):923-36.
PMID 10946852
Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC.
Hu YC, Lam KY, Law S, Wong J, Srivastava G.
Clin Cancer Res. 2001 Aug;7(8):2213-21.
PMID 11489794
Transcription factor Fra-1 induces cholangitis and liver fibrosis.
Kireva T, Erhardt A, Tiegs G, Tilg H, Denk H, Haybaeck J, Aigner E, Moschen A, Distler JH, Schett G, Zwerina J.
Hepatology. 2011 Apr;53(4):1259-69. doi: 10.1002/hep.24175.
PMID 21480331
Epstein-Barr virus latent membrane protein 2A promotes invasion of nasopharyngeal carcinoma cells through ERK/Fra-1-mediated induction of matrix metalloproteinase 9.
Lan YY, Hsiao JR, Chang KC, Chang JS, Chen CW, Lai HC, Wu SY, Yeh TH, Chang FH, Lin WH, Su IJ, Chang Y.
J Virol. 2012 Jun;86(12):6656-67. doi: 10.1128/JVI.00174-12. Epub 2012 Apr 18.
PMID 22514348
Role of Fos-related antigen 1 in the progression and prognosis of ductal breast carcinoma.
Logullo AF, Stiepcich MM, Osorio CA, Nonogaki S, Pasini FS, Rocha RM, Soares FA, Brentani MM.
Histopathology. 2011 Mar;58(4):617-25. doi: 10.1111/j.1365-2559.2011.03785.x. Epub 2011 Mar 3.
PMID 21371080
Fra-1 promotes breast cancer chemosensitivity by driving cancer stem cells from dormancy.
Lu D, Chen S, Tan X, Li N, Liu C, Li Z, Liu Z, Stupack DG, Reisfeld RA, Xiang R.
Cancer Res. 2012 Jul 15;72(14):3451-6. doi: 10.1158/0008-5472.CAN-11-2536. Epub 2012 May 14.
PMID 22586064
A DNA vaccine targeting Fos-related antigen 1 enhanced by IL-18 induces long-lived T-cell memory against tumor recurrence.
Luo Y, Zhou H, Mizutani M, Mizutani N, Liu C, Xiang R, Reisfeld RA.
Cancer Res. 2005 Apr 15;65(8):3419-27.
PMID 15833877
The role of proto-oncogene Fra-1 in remodeling the tumor microenvironment in support of breast tumor cell invasion and progression.
Luo YP, Zhou H, Krueger J, Kaplan C, Liao D, Markowitz D, Liu C, Chen T, Chuang TH, Xiang R, Reisfeld RA.
Oncogene. 2010 Feb 4;29(5):662-73. doi: 10.1038/onc.2009.308. Epub 2009 Dec 7.
PMID 19966854
Expression and significance of FRA-1 in non-small-cell lung cancer.
Ma K, Chang D, Gong M, Ding F, Luo A, Tian F, Liu Z, Wang T.
Cancer Invest. 2009 Mar;27(3):353-9. doi: 10.1080/07357900802254008.
PMID 19160107
Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinoma.
Mangone FR, Brentani MM, Nonogaki S, Begnami MD, Campos AH, Walder F, Carvalho MB, Soares FA, Torloni H, Kowalski LP, Federico MH.
Int J Exp Pathol. 2005 Aug;86(4):205-12.
PMID 16045542
Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation.
Matsuo K, Owens JM, Tonko M, Elliott C, Chambers TJ, Wagner EF.
Nat Genet. 2000 Feb;24(2):184-7.
PMID 10655067
Inhibition of FOSL1 overexpression in antiestrogen-resistant MCF-7 cells decreases cell growth and increases vacuolization and cell death.
Pennanen PT, Sarvilinna NS, Toimela T, Ylikomi TJ.
Steroids. 2011 Sep-Oct;76(10-11):1063-8. doi: 10.1016/j.steroids.2011.04.011. Epub 2011 May 5.
PMID 21570421
FRA-1 expression level modulates regulation of activator protein-1 activity by estradiol in breast cancer cells.
Philips A, Teyssier C, Galtier F, Rivier-Covas C, Rey JM, Rochefort H, Chalbos D.
Mol Endocrinol. 1998 Jul;12(7):973-85.
PMID 9658402
Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo.
Rajasekaran S, Vaz M, Reddy SP.
PLoS One. 2012;7(7):e41611. doi: 10.1371/journal.pone.0041611. Epub 2012 Jul 24.
PMID 22911824
Normal mineralization and nanostructure of sclerotic bone in mice overexpressing Fra-1.
Roschger P, Matsuo K, Misof BM, Tesch W, Jochum W, Wagner EF, Fratzl P, Klaushofer K.
Bone. 2004 May;34(5):776-82.
PMID 15121008
NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.
Sandford AJ, Malhotra D, Boezen HM, Siedlinski M, Postma DS, Wong V, Akhabir L, He JQ, Connett JE, Anthonisen NR, Pare PD, Biswal S.
Physiol Genomics. 2012 Aug 1;44(15):754-63. doi: 10.1152/physiolgenomics.00027.2012. Epub 2012 Jun 12.
PMID 22693272
Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL.
Sayan AE, Stanford R, Vickery R, Grigorenko E, Diesch J, Kulbicki K, Edwards R, Pal R, Greaves P, Jariel-Encontre I, Piechaczyk M, Kriajevska M, Mellon JK, Dhillon AS, Tulchinsky E.
Oncogene. 2012 Mar 22;31(12):1493-503. doi: 10.1038/onc.2011.336. Epub 2011 Aug 8.
PMID 21822309
Overexpression of the immediate early gene fra-1 inhibits proliferation, induces apoptosis, and reduces tumourigenicity of c6 glioma cells.
Shirsat NV, Shaikh SA.
Exp Cell Res. 2003 Nov 15;291(1):91-100.
PMID 14597411
An association of a simultaneous nuclear and cytoplasmic localization of Fra-1 with breast malignancy.
Song Y, Song S, Zhang D, Zhang Y, Chen L, Qian L, Shi M, Zhao H, Jiang Z, Guo N.
BMC Cancer. 2006 Dec 28;6:298.
PMID 17192200
Interstitial lung disease induced by gefitinib and toll-like receptor ligands is mediated by Fra-1.
Takada Y, Gresh L, Bozec A, Ikeda E, Kamiya K, Watanabe M, Kobayashi K, Asano K, Toyama Y, Wagner EF, Matsuo K.
Oncogene. 2011 Sep 8;30(36):3821-32. doi: 10.1038/onc.2011.101. Epub 2011 Apr 4.
PMID 21460858
Gene expression profiling in prostate cancer cells with Akt activation reveals Fra-1 as an Akt-inducible gene.
Tiwari G, Sakaue H, Pollack JR, Roth RA.
Mol Cancer Res. 2003 Apr;1(6):475-84.
PMID 12692267
The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma.
Usui A, Hoshino I, Akutsu Y, Sakata H, Nishimori T, Murakami K, Kano M, Shuto K, Matsubara H.
Cancer. 2012 Jul 1;118(13):3387-96. doi: 10.1002/cncr.26652. Epub 2011 Oct 25.
PMID 22028113
Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.
Vallone D, Battista S, Pierantoni GM, Fedele M, Casalino L, Santoro M, Viglietto G, Fusco A, Verde P.
EMBO J. 1997 Sep 1;16(17):5310-21.
PMID 9311991
Genetic disruption of Fra-1 decreases susceptibility to endotoxin-induced acute lung injury and mortality in mice.
Vaz M, Reddy NM, Rajasekaran S, Reddy SP.
Am J Respir Cell Mol Biol. 2012 Jan;46(1):55-62. doi: 10.1165/rcmb.2011-0169OC.
PMID 21816965
Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters.
Verde P, Casalino L, Talotta F, Yaniv M, Weitzman JB.
Cell Cycle. 2007 Nov 1;6(21):2633-9. Epub 2007 Aug 8. (REVIEW)
PMID 17957143
Elevated ERK-MAP kinase activity protects the FOS family member FRA-1 against proteasomal degradation in colon carcinoma cells.
Vial E, Marshall CJ.
J Cell Sci. 2003 Dec 15;116(Pt 24):4957-63.
PMID 14625389
Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c-Myc in human colorectal adenocarcinomas overexpressing beta-catenin.
Wang HL, Wang J, Xiao SY, Haydon R, Stoiber D, He TC, Bissonnette M, Hart J.
Int J Cancer. 2002 Oct 1;101(4):301-10.
PMID 12209953
MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1.
Wu J, Wu G, Lv L, Ren YF, Zhang XJ, Xue YF, Li G, Lu X, Sun Z, Tang KF.
Carcinogenesis. 2012 Mar;33(3):519-28. doi: 10.1093/carcin/bgr304. Epub 2011 Dec 22.
PMID 22198213
MicroRNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1.
Yang S, Li Y, Gao J, Zhang T, Li S, Luo A, Chen H, Ding F, Wang X, Liu Z.
Oncogene. 2012 Sep 24. doi: 10.1038/onc.2012.432. [Epub ahead of print]
PMID 23001043
Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently.
Young MR, Nair R, Bucheimer N, Tulsian P, Brown N, Chapp C, Hsu TC, Colburn NH.
Mol Cell Biol. 2002 Jan;22(2):587-98.
PMID 11756554
Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer.
Zerbini LF, Wang Y, Cho JY, Libermann TA.
Cancer Res. 2003 May 1;63(9):2206-15.
PMID 12727841
Differential expression of the AP-1 transcription factor family members in human colorectal epithelial and neuroendocrine neoplasms.
Zhang W, Hart J, McLeod HL, Wang HL.
Am J Clin Pathol. 2005 Jul;124(1):11-9.
PMID 15923159
PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation.
Zippo A, De Robertis A, Serafini R, Oliviero S.
Nat Cell Biol. 2007 Aug;9(8):932-44. Epub 2007 Jul 22.
PMID 17643117


This paper should be referenced as such :
Rajamohan, SB ; Reddy, SP
FOSL1 (FOS-like antigen 1)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(5):313-318.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(14;19)(q32;q13) IGH::Various Partners

External links


HGNC (Hugo)FOSL1   13718
Entrez_Gene (NCBI)FOSL1    FOS like 1, AP-1 transcription factor subunit
AliasesFRA; FRA1; fra-1
GeneCards (Weizmann)FOSL1
Ensembl hg19 (Hinxton)ENSG00000175592 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000175592 [Gene_View]  ENSG00000175592 [Sequence]  chr11:65892049-65900388 [Contig_View]  FOSL1 [Vega]
ICGC DataPortalENSG00000175592
TCGA cBioPortalFOSL1
Genatlas (Paris)FOSL1
SOURCE (Princeton)FOSL1
Genetics Home Reference (NIH)FOSL1
Genomic and cartography
GoldenPath hg38 (UCSC)FOSL1  -     chr11:65892049-65900388 -  11q13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FOSL1  -     11q13.1   [Description]    (hg19-Feb_2009)
GoldenPathFOSL1 - 11q13.1 [CytoView hg19]  FOSL1 - 11q13.1 [CytoView hg38]
Genome Data Viewer NCBIFOSL1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AA120824 AK222902 AK293297 AK299050 AK313718
RefSeq transcript (Entrez)NM_001300844 NM_001300855 NM_001300856 NM_001300857 NM_005438
Consensus coding sequences : CCDS (NCBI)FOSL1
Gene ExpressionFOSL1 [ NCBI-GEO ]   FOSL1 [ EBI - ARRAY_EXPRESS ]   FOSL1 [ SEEK ]   FOSL1 [ MEM ]
Gene Expression Viewer (FireBrowse)FOSL1 [ Firebrowse - Broad ]
GenevisibleExpression of FOSL1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8061
GTEX Portal (Tissue expression)FOSL1
Human Protein AtlasENSG00000175592-FOSL1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP15407   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP15407  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP15407
Domaine pattern : Prosite (Expaxy)BZIP (PS50217)    BZIP_BASIC (PS00036)   
Domains : Interpro (EBI)AP-1    bZIP    Fra1   
Domain families : Pfam (Sanger)bZIP_1 (PF00170)   
Domain families : Pfam (NCBI)pfam00170   
Domain families : Smart (EMBL)BRLZ (SM00338)  
Conserved Domain (NCBI)FOSL1
AlphaFold pdb e-kbP15407   
Human Protein Atlas [tissue]ENSG00000175592-FOSL1 [tissue]
Protein Interaction databases
IntAct (EBI)P15407
Ontologies - Pathways
Ontology : AmiGOchromatin  RNA polymerase II cis-regulatory region sequence-specific DNA binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  in utero embryonic development  DNA-binding transcription factor activity  protein binding  nucleus  nucleoplasm  cytosol  regulation of transcription by RNA polymerase II  chemotaxis  cellular defense response  vitellogenesis  female pregnancy  learning  positive regulation of cell population proliferation  negative regulation of cell population proliferation  response to mechanical stimulus  response to virus  response to gravity  cellular response to extracellular stimulus  response to progesterone  response to cytokine  response to drug  response to hydrogen peroxide  presynaptic membrane  neuron projection  positive regulation of apoptotic process  positive regulation of cell cycle  positive regulation of DNA-binding transcription factor activity  response to corticosterone  response to cAMP  placenta blood vessel development  positive regulation of pri-miRNA transcription by RNA polymerase II  sequence-specific double-stranded DNA binding  positive regulation of DNA-templated transcription, initiation  
Ontology : EGO-EBIchromatin  RNA polymerase II cis-regulatory region sequence-specific DNA binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  in utero embryonic development  DNA-binding transcription factor activity  protein binding  nucleus  nucleoplasm  cytosol  regulation of transcription by RNA polymerase II  chemotaxis  cellular defense response  vitellogenesis  female pregnancy  learning  positive regulation of cell population proliferation  negative regulation of cell population proliferation  response to mechanical stimulus  response to virus  response to gravity  cellular response to extracellular stimulus  response to progesterone  response to cytokine  response to drug  response to hydrogen peroxide  presynaptic membrane  neuron projection  positive regulation of apoptotic process  positive regulation of cell cycle  positive regulation of DNA-binding transcription factor activity  response to corticosterone  response to cAMP  placenta blood vessel development  positive regulation of pri-miRNA transcription by RNA polymerase II  sequence-specific double-stranded DNA binding  positive regulation of DNA-templated transcription, initiation  
Pathways : BIOCARTABone Remodelling [Genes]   
Pathways : KEGGWnt signaling pathway    Osteoclast differentiation    HTLV-I infection   
NDEx NetworkFOSL1
Atlas of Cancer Signalling NetworkFOSL1
Wikipedia pathwaysFOSL1
Orthology - Evolution
GeneTree (enSembl)ENSG00000175592
Phylogenetic Trees/Animal Genes : TreeFamFOSL1
Homologs : HomoloGeneFOSL1
Homology/Alignments : Family Browser (UCSC)FOSL1
Gene fusions - Rearrangements
Fusion : QuiverFOSL1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFOSL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FOSL1
Exome Variant ServerFOSL1
GNOMAD BrowserENSG00000175592
Varsome BrowserFOSL1
ACMGFOSL1 variants
Genomic Variants (DGV)FOSL1 [DGVbeta]
DECIPHERFOSL1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFOSL1 
ICGC Data PortalFOSL1 
TCGA Data PortalFOSL1 
Broad Tumor PortalFOSL1
OASIS PortalFOSL1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFOSL1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DFOSL1
Mutations and Diseases : HGMDFOSL1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)FOSL1
DoCM (Curated mutations)FOSL1
CIViC (Clinical Interpretations of Variants in Cancer)FOSL1
NCG (London)FOSL1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry FOSL1
NextProtP15407 [Medical]
Target ValidationFOSL1
Huge Navigator FOSL1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDFOSL1
Pharm GKB GenePA28214
Pharm GKB PathwaysPA165985892   
Clinical trialFOSL1
DataMed IndexFOSL1
PubMed160 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:18:13 CEST 2021

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