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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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No annotation is available in this section for this article. The content below is taken from a related TF, FOSL1 (Homo sapiens).

Genetic disruption studies in mice have shown that FOSL1 is critical for extra-embryonic tissue development.[1] However, mice lacking this transcription factor, specifically in the embryo, develop normally without an overt phenotype and the mice subsequently display reduced bone mass formation and osteopenia. [2] Genetic complementation studies in mice have shown an overlapping function between FOSL1 and FOS in bone growth.[2][3] Transgenic overexpression of FOSL1 under the control of a ubiquitous promoter stimulates increased bone formation and osteosclerosis in mice.[4]. Recently, FOSL1 has been shown to impair inflammation and chondrogenesis in fracture healing.[5] FOSL1 is situated at position 11q13. No genetic mutations leading to activation or inactivation of this transcription factor in human disease development and in malignancies have yet been documented, although human genome sequencing analysis revealed the existence of single nucleotide polymorphisms (SNPs) in FOSL1. Increased levels of FOSL1 mRNA transcripts, however, have been detected in various tumor tissues such as breast, lung, brain, thyroid, prostate, colon, head and neck, esophagus and stomach as well as in glioblastomas and mesotheliomas. [6][7][8][9][10][11] For more details see reviews.[12][13] FOSL1 plays an important role in human cancer cell survival and proliferation as well as progression [14]. Ectopic FOSL1 expression induces motility and invasion as well as the maintenance and progression of the transformed state in several cancer cell types,[15] while silencing or knockdown of FOSL1 expression reverses these malignant phenotypes. [16][17][18][19][20][21] FOSL1 regulates cell survival and proliferation in different cell types.[21][22] Moreover, several studies have shown that various carcinogens, such as asbestos and cigarette smoke, strongly induce FOSL1 expression in epithelial cells. This induction occurs mainly through EGFR-activated Ras signaling,[23][24][25] which is frequently mutated in human lung tumors and is known to promote tumor initiation and development as well as progression in vivo. [26] Recently, FOSL1-based DNA vaccines have been used to target breast and lung tumor growth and metastasis.[27] Moreover, FOSL1 expression is induced by various stressful and toxic (non-carcinogenic) stimuli and by various mitogens and cytokines in various cell types.[28][14][29] Several studies performed in cell culture studies illuminate a potential role for FOSL1 both in physiologic and pathophysiologic processes; however, further studies using "floxed" mice are warranted to dissect the exact role(s) of this proto-oncogene in the development and progression of various malignant and nonmalignant diseases in vivo.

  1. Schreiber M et al. Placental vascularisation requires the AP-1 component fra1. Development, 127(22):4937-48. (PMID 11044407)
  2. Eferl R et al. The Fos-related antigen Fra-1 is an activator of bone matrix formation. EMBO J., 23(14):2789-99. (PMID 15229648)
  3. Fleischmann A et al. Fra-1 replaces c-Fos-dependent functions in mice. Genes Dev., 14(21):2695-700. (PMID 11069886)
  4. Jochum W et al. Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Nat. Med., 6(9):980-4. (PMID 10973316)
  5. Yamaguchi T et al. Fra-1/AP-1 Impairs Inflammatory Responses and Chondrogenesis in Fracture Healing. J. Bone Miner. Res. (PMID 19558315)
  6. Risse-Hackl G et al. Transition from SCLC to NSCLC phenotype is accompanied by an increased TRE-binding activity and recruitment of specific AP-1 proteins. Oncogene, 16(23):3057-68. (PMID 9662339)
  7. Hu YC et al. 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. Clin. Cancer Res., 7(8):2213-21. (PMID 11489794)
  8. Mangone FR et al. Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinoma. , 86(4):205-12. (PMID 16045542)
  9. Song Y et al. An association of a simultaneous nuclear and cytoplasmic localization of Fra-1 with breast malignancy. BMC Cancer, 6:298. (PMID 17192200)
  10. Debinski W and Gibo DM. Fos-related antigen 1 modulates malignant features of glioma cells. Mol. Cancer Res., 3(4):237-49. (PMID 15831677)
  11. Chiappetta G et al. FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders. BMC Cancer, 7:17. (PMID 17254320)
  12. Tulchinsky E. Fos family members: regulation, structure and role in oncogenic transformation. Histol. Histopathol., 15(3):921-8. (PMID 10963134)
  13. Milde-Langosch K. The Fos family of transcription factors and their role in tumourigenesis. Eur. J. Cancer, 41(16):2449-61. (PMID 16199154)
  14. Verde P et al. Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters. Cell Cycle, 6(21):2633-9. (PMID 17957143)
  15. Bergers G et al. Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron. Mol. Cell. Biol., 15(7):3748-58. (PMID 7791782)
  1. Kustikova O et al. Fra-1 induces morphological transformation and increases in vitro invasiveness and motility of epithelioid adenocarcinoma cells. Mol. Cell. Biol., 18(12):7095-105. (PMID 9819396)
  2. Adiseshaiah P et al. FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but is insufficient to promote tumor growth in vivo. Cancer Res., 67(13):6204-11. (PMID 17616677)
  3. Vial E et al. ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell, 4(1):67-79. (PMID 12892714)
  4. Ramos-Nino ME et al. Mesothelial cell transformation requires increased AP-1 binding activity and ERK-dependent Fra-1 expression. Cancer Res., 62(21):6065-9. (PMID 12414630)
  5. Ramos-Nino ME et al. Fra-1 governs cell migration via modulation of CD44 expression in human mesotheliomas. Mol. Cancer, 6:81. (PMID 18096084)
  6. Belguise K et al. FRA-1 expression level regulates proliferation and invasiveness of breast cancer cells. Oncogene, 24(8):1434-44. (PMID 15608675)
  7. Casalino L et al. Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription. EMBO J., 26(7):1878-90. (PMID 17347653)
  8. Zhang Q et al. Matrix metalloproteinase/epidermal growth factor receptor/mitogen-activated protein kinase signaling regulate fra-1 induction by cigarette smoke in lung epithelial cells. Am. J. Respir. Cell Mol. Biol., 32(1):72-81. (PMID 15528491)
  9. Scapoli L et al. Src-dependent ERK5 and Src/EGFR-dependent ERK1/2 activation is required for cell proliferation by asbestos. Oncogene, 23(3):805-13. (PMID 14737115)
  10. Zhang Q et al. A Phosphatidylinositol 3-kinase-regulated Akt-independent signaling promotes cigarette smoke-induced FRA-1 expression. J. Biol. Chem., 281(15):10174-81. (PMID 16490785)
  11. Roberts PJ and Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene, 26(22):3291-310. (PMID 17496923)
  12. Xiang R et al. Oral DNA vaccines target the tumor vasculature and microenvironment and suppress tumor growth and metastasis. Immunol. Rev., 222:117-28. (PMID 18363997)
  13. Reddy SP and Mossman BT. Role and regulation of activator protein-1 in toxicant-induced responses of the lung. Am. J. Physiol. Lung Cell Mol. Physiol., 283(6):L1161-78. (PMID 12424143)
  14. Young MR and Colburn NH. Fra-1 a target for cancer prevention or intervention. Gene, 379:1-11. (PMID 16784822)
MeSH cloud (automatically populated)
About this section
The MeSH cloud below displays MeSH terms that are associated with this transcription factor. The physical size of the terms reflect the significance of their association with the transcription factor as determined by the Fisher's Exact Test. It should be noted that these associations do not necessarily imply a positive correlation between the described MeSH term and this transcription factor. For instance, if the MeSH term "apoptosis" occurs, it may indicate that this transcription factor can induce apoptosis (positive correlation), or prevent apoptosis (negative correlation). Methods: The transcription factor is mapped to a set of Pubmed publications through the gene-to-pubmed association as provided by NCBI. Then, a collection of MeSH terms associated with the papers are compiled, along with the frequency of each MeSH term. The Fisher's Exact Test is conducted on the frequency of each term in the collection, versus its average frequency, to determine its significance in the collection. More information on MeSH can be found on the MeSH homepage.
MeSH term Fisher's exact p-value
1 Osteopetrosis 7.6 x 10-6
2 Embryo Loss 0.0015
3 Disease Models, Animal 0.018
4 Fetal Growth Retardation 0.019
5 Cardiomyopathy, Dilated 0.019
6 Dwarfism 0.022
7 Pulmonary Emphysema 0.023
8 Retinal Degeneration 0.040
9 Fetal Death 0.041
10 Bone Resorption 0.047
MeSH term Fisher's exact p-value
1 Osteosclerosis 1.8 x 10-10
2 Bone Diseases, Developmental 7.4 x 10-8
3 Osteochondrodysplasias 8.3 x 10-8
4 Bone Diseases 2.6 x 10-6
5 Osteopetrosis 7.6 x 10-6
6 Musculoskeletal Diseases 3.5 x 10-5
7 Embryo Loss 0.0015
8 Death 0.014
9 Disease Models, Animal 0.018
10 Fetal Growth Retardation 0.019
11 Cardiomyopathy, Dilated 0.019
12 Dwarfism 0.022
13 Pulmonary Emphysema 0.023
14 Animal Diseases 0.035
15 Retinal Degeneration 0.040
16 Fetal Death 0.041
17 Growth Disorders 0.044
18 Abortion, Spontaneous 0.046
19 Bone Resorption 0.047