Biology:FLI1
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Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the FLI1 gene, which is a proto-oncogene.[1][2][3]
Function
Fli-1 is a member of the ETS transcription factor family that was first identified in erythroleukemias induced by Friend Murine Leukemia Virus (F-MuLV). Fli-1 is activated through retroviral insertional mutagenesis in 90% of F-MuLV-induced erythroleukemias. The constitutive activation of fli-1 in erythroblasts leads to a dramatic shift in the Epo/Epo-R signal transduction pathway, blocking erythroid differentiation, activating the Ras pathway, and resulting in massive Epo-independent proliferation of erythroblasts. These results suggest that Fli-1 overexpression in erythroblasts alters their responsiveness to Epo and triggers abnormal proliferation by switching the signaling event(s) associated with terminal differentiation to proliferation. [citation needed]
Clinical significance
In addition to Friend erythroleukemia, proviral integration at the fli-1 locus also occurs in leukemias induced by the 10A1, Graffi, and Cas-Br-E viruses. Fli-1 aberrant expression is also associated with chromosomal abnormalities in humans. In pediatric Ewing’s sarcoma a chromosomal translocation generates a fusion of the 5’ transactivation domain of EWSR1 (also known as EWS) with the 3’ Ets domain of Fli-1. The resulting fusion oncoprotein, EWS/Fli-1, acts as an aberrant transcriptional activator.[4] with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with enhancer-like GGAA-microsatellites.[5] The importance of Fli-1 in the development of human leukemia, such as acute myelogenous leukemia (AML), has been demonstrated in studies of translocation involving the Tel transcription factor, which interacts with Fli-1 through protein-protein interactions. A recent study has demonstrated high levels of Fli-1 expression in several benign and malignant neoplasms using immunohistochemistry.[citation needed]
A possible association with Paris-Trousseau syndrome has been suggested.[6]
References
- ↑ "The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24". Genomics 11 (1): 223–4. September 1991. doi:10.1016/0888-7543(91)90124-W. PMID 1765382.
- ↑ "Structure and expression of human Fli-1 gene". Cancer Research 52 (20): 5833–7. October 1992. PMID 1394211.
- ↑ "Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein". Oncogene 8 (8): 2167–73. August 1993. PMID 8336942.
- ↑ "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Research 53 (24): 5859–63. December 1993. PMID 7503813.
- ↑ Musa, Julian et al. (2018-12-27). "Cooperation of dominant oncogenes with regulatory germline variants shapes clinical outcomes in childhood cancer" (in en). bioRxiv: 506659. doi:10.1101/506659. https://www.biorxiv.org/content/early/2018/12/27/506659.
- ↑ "FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia". The Journal of Clinical Investigation 114 (1): 77–84. July 2004. doi:10.1172/JCI21197. PMID 15232614.
Further reading
- "Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus". Proceedings of the National Academy of Sciences of the United States of America 87 (4): 1332–6. February 1990. doi:10.1073/pnas.87.4.1332. PMID 2304901. Bibcode: 1990PNAS...87.1332B.
- "Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1". Genes & Development 5 (6): 908–18. June 1991. doi:10.1101/gad.5.6.908. PMID 2044959.
- "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature 359 (6391): 162–5. September 1992. doi:10.1038/359162a0. PMID 1522903. Bibcode: 1992Natur.359..162D.
- "FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts". Oncogene 18 (8): 1597–608. February 1999. doi:10.1038/sj.onc.1202534. PMID 10102630.
- "Fli-1, an Ets-related transcription factor, regulates erythropoietin-induced erythroid proliferation and differentiation: evidence for direct transcriptional repression of the Rb gene during differentiation". Molecular and Cellular Biology 19 (6): 4452–64. June 1999. doi:10.1128/mcb.19.6.4452. PMID 10330185.
- "Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia". Oncogene 19 (19): 2296–304. May 2000. doi:10.1038/sj.onc.1203590. PMID 10822380.
- "Spi-1/PU.1 is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines". Molecular and Cellular Biology 19 (1): 121–35. January 1999. doi:10.1128/mcb.19.1.121. PMID 9858537.
- "The role of Fli-1 in normal cell function and malignant transformation". Oncogene 19 (55): 6482–9. December 2000. doi:10.1038/sj.onc.1204042. PMID 11175364.
- "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Research 53 (24): 5859–63. December 1993. PMID 7503813.
- "Fli-1b is generated by usage of differential splicing and alternative promoter". Oncogene 17 (9): 1149–57. September 1998. doi:10.1038/sj.onc.1202030. PMID 9764825.
- "Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein". Oncogene 8 (8): 2167–73. August 1993. PMID 8336942.
- "Ews-Fli1 in Ewing's Sarcoma: Real Targets and Collateral Damage". New trends in cancer for the 21st century. Advances in Experimental Medicine and Biology. 587. 2006. pp. 41–52. doi:10.1007/978-1-4020-5133-3_4. ISBN 978-1-4020-4966-8.
- "Structure and expression of human Fli-1 gene". Cancer Research 52 (20): 5833–7. October 1992. PMID 1394211.
- "The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors". Cell Growth & Differentiation 3 (10): 705–13. October 1992. PMID 1445800.
- "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature 359 (6391): 162–5. September 1992. doi:10.1038/359162a0. PMID 1522903. Bibcode: 1992Natur.359..162D.
- "The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24". Genomics 11 (1): 223–4. September 1991. doi:10.1016/0888-7543(91)90124-W. PMID 1765382.
- "Identification of a common viral integration region in Cas-Br-E murine leukemia virus-induced non-T-, non-B-cell lymphomas". Journal of Virology 65 (1): 7–15. January 1991. doi:10.1128/JVI.65.1.7-15.1991. PMID 1845910.
- "Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma". Genes, Chromosomes & Cancer 13 (2): 126–32. June 1995. doi:10.1002/gcc.2870130209. PMID 7542907.
- "Solution structure of the ets domain of Fli-1 when bound to DNA". Nature Structural Biology 1 (12): 871–5. December 1994. doi:10.1038/nsb1294-871. PMID 7773776.
- "The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1". Molecular and Cellular Biology 13 (12): 7393–8. December 1993. doi:10.1128/mcb.13.12.7393. PMID 8246959.
- "Human FLI-1 localizes to chromosome 11Q24 and has an aberrant transcript in neuroepithelioma". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1172 (1–2): 155–8. February 1993. doi:10.1016/0167-4781(93)90283-J. PMID 8439553.
- "SRE elements are binding sites for the fusion protein EWS-FLI-1". Nucleic Acids Research 24 (6): 1052–8. March 1996. doi:10.1093/nar/24.6.1052. PMID 8604338.
- "Characterization of the human and mouse Fli-1 promoter regions". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1307 (2): 220–32. June 1996. doi:10.1016/0167-4781(96)00060-7. PMID 8679708.
- "FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements". Oncogene 14 (2): 213–21. January 1997. doi:10.1038/sj.onc.1200839. PMID 9010223.
- "The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity". The Journal of Biological Chemistry 273 (28): 17525–30. July 1998. doi:10.1074/jbc.273.28.17525. PMID 9651344.
- "Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains". Oncogene 16 (25): 3261–8. June 1998. doi:10.1038/sj.onc.1201868. PMID 9681824.
- "Chromosome translocation based on illegitimate recombination in human tumors". Proceedings of the National Academy of Sciences of the United States of America 95 (20): 11786–91. September 1998. doi:10.1073/pnas.95.20.11786. PMID 9751743. Bibcode: 1998PNAS...9511786Z.
- "The mechanism of complex formation between Fli-1 and SRF transcription factors". Nucleic Acids Research 28 (2): 560–9. January 2000. doi:10.1093/nar/28.2.560. PMID 10606656.
- "The splicing factor U1C represses EWS/FLI-mediated transactivation". The Journal of Biological Chemistry 275 (32): 24865–71. August 2000. doi:10.1074/jbc.M001661200. PMID 10827180.
- "Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor". Molecular and Cellular Biology 20 (15): 5643–52. August 2000. doi:10.1128/MCB.20.15.5643-5652.2000. PMID 10891501.
- "A novel zinc finger gene is fused to EWS in small round cell tumor". Oncogene 19 (33): 3799–804. August 2000. doi:10.1038/sj.onc.1203762. PMID 10949935.
External links
- FLI1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
![]() | Original source: https://en.wikipedia.org/wiki/FLI1.
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