FLI1

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|date=December 2010}}

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.{{cite journal | vauthors = Ohno T, Rao VN, Reddy ES | title = EWS/Fli-1 chimeric protein is a transcriptional activator | journal = Cancer Research | volume = 53 | issue = 24 | pages = 5859–63 | date = December 1993 | pmid = 7503813 }} with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with enhancer-like GGAA-microsatellites.{{Cite journal| vauthors = Musa J, Cidre-Aranaz F, Aynaud MM, Orth MF, Mirabeau O, Varon M, Grossetête S, Surdez D, Ohmura S, Gerke JS, Marchetto A |date=2018-12-27|title=Cooperation of dominant oncogenes with regulatory germline variants shapes clinical outcomes in childhood cancer|url=https://www.biorxiv.org/content/early/2018/12/27/506659|journal=bioRxiv|language=en|pages=506659|doi=10.1101/506659|doi-access=free}} 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|date=December 2010}}

A possible association with Paris-Trousseau syndrome has been suggested.{{cite journal | vauthors = Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, Danos O, Albagli O, Vainchenker W, Favier R | display-authors = 6 | title = FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia | journal = The Journal of Clinical Investigation | volume = 114 | issue = 1 | pages = 77–84 | date = July 2004 | pmid = 15232614 | pmc = 437972 | doi = 10.1172/JCI21197 }}

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• {{cite journal | vauthors = Ben-David Y, Giddens EB, Bernstein A | title = Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 4 | pages = 1332–6 | date = February 1990 | pmid = 2304901 | pmc = 53469 | doi = 10.1073/pnas.87.4.1332 | bibcode = 1990PNAS...87.1332B | doi-access = free }}
• {{cite journal | vauthors = Ben-David Y, Giddens EB, Letwin K, Bernstein A | title = 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 | journal = Genes & Development | volume = 5 | issue = 6 | pages = 908–18 | date = June 1991 | pmid = 2044959 | doi = 10.1101/gad.5.6.908 | doi-access = free }}
• {{cite journal | vauthors = Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G | display-authors = 6 | title = Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours | journal = Nature | volume = 359 | issue = 6391 | pages = 162–5 | date = September 1992 | pmid = 1522903 | doi = 10.1038/359162a0 | bibcode = 1992Natur.359..162D | s2cid = 4331584 }}
• {{cite journal | vauthors = Pereira R, Quang CT, Lesault I, Dolznig H, Beug H, Ghysdael J | title = FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts | journal = Oncogene | volume = 18 | issue = 8 | pages = 1597–608 | date = February 1999 | pmid = 10102630 | doi = 10.1038/sj.onc.1202534 | s2cid = 25190024 | doi-access = }}
• {{cite journal | vauthors = Tamir A, Howard J, Higgins RR, Li YJ, Berger L, Zacksenhaus E, Reis M, Ben-David Y | display-authors = 6 | title = 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 | journal = Molecular and Cellular Biology | volume = 19 | issue = 6 | pages = 4452–64 | date = June 1999 | pmid = 10330185 | pmc = 104404 | doi = 10.1128/mcb.19.6.4452 }}
• {{cite journal | vauthors = Zochodne B, Truong AH, Stetler K, Higgins RR, Howard J, Dumont D, Berger SA, Ben-David Y | display-authors = 6 | title = Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia | journal = Oncogene | volume = 19 | issue = 19 | pages = 2296–304 | date = May 2000 | pmid = 10822380 | doi = 10.1038/sj.onc.1203590 | s2cid = 7468572 | doi-access = }}
• {{cite journal | vauthors = Starck J, Doubeikovski A, Sarrazin S, Gonnet C, Rao G, Skoultchi A, Godet J, Dusanter-Fourt I, Morle F | display-authors = 6 | title = Spi-1/PU.1 is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines | journal = Molecular and Cellular Biology | volume = 19 | issue = 1 | pages = 121–35 | date = January 1999 | pmid = 9858537 | pmc = 83871 | doi = 10.1128/mcb.19.1.121 }}
• {{cite journal | vauthors = Truong AH, Ben-David Y | title = The role of Fli-1 in normal cell function and malignant transformation | journal = Oncogene | volume = 19 | issue = 55 | pages = 6482–9 | date = December 2000 | pmid = 11175364 | doi = 10.1038/sj.onc.1204042 | s2cid = 28146474 | doi-access = }}
• {{cite journal | vauthors = Ohno T, Rao VN, Reddy ES | title = EWS/Fli-1 chimeric protein is a transcriptional activator | journal = Cancer Research | volume = 53 | issue = 24 | pages = 5859–63 | date = December 1993 | pmid = 7503813 }}
• {{cite journal | vauthors = Dhulipala PD, Lee L, Rao VN, Reddy ES | title = Fli-1b is generated by usage of differential splicing and alternative promoter | journal = Oncogene | volume = 17 | issue = 9 | pages = 1149–57 | date = September 1998 | pmid = 9764825 | doi = 10.1038/sj.onc.1202030 | doi-access = free }}
• {{cite journal | vauthors = Rao VN, Ohno T, Prasad DD, Bhattacharya G, Reddy ES | title = Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein | journal = Oncogene | volume = 8 | issue = 8 | pages = 2167–73 | date = August 1993 | pmid = 8336942 }}
• {{cite book | vauthors = Ban J, Siligan C, Kreppel M, Aryee D, Kovar H | title = New trends in cancer for the 21st century | chapter = Ews-Fli1 in Ewing's Sarcoma: Real Targets and Collateral Damage | series = Advances in Experimental Medicine and Biology | date = 2006 | volume = 587 | pages = 41–52 | pmid = 17163154 | doi = 10.1007/978-1-4020-5133-3_4 | isbn = 978-1-4020-4966-8 }}
• {{cite journal | vauthors = Prasad DD, Rao VN, Reddy ES | title = Structure and expression of human Fli-1 gene | journal = Cancer Research | volume = 52 | issue = 20 | pages = 5833–7 | date = October 1992 | pmid = 1394211 }}
• {{cite journal | vauthors = Watson DK, Smyth FE, Thompson DM, Cheng JQ, Testa JR, Papas TS, Seth A | title = The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors | journal = Cell Growth & Differentiation | volume = 3 | issue = 10 | pages = 705–13 | date = October 1992 | pmid = 1445800 }}
• {{cite journal | vauthors = Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G | display-authors = 6 | title = Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours | journal = Nature | volume = 359 | issue = 6391 | pages = 162–5 | date = September 1992 | pmid = 1522903 | doi = 10.1038/359162a0 | bibcode = 1992Natur.359..162D | s2cid = 4331584 }}
• {{cite journal | vauthors = Baud V, Lipinski M, Rassart E, Poliquin L, Bergeron D | title = The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24 | journal = Genomics | volume = 11 | issue = 1 | pages = 223–4 | date = September 1991 | pmid = 1765382 | doi = 10.1016/0888-7543(91)90124-W }}
• {{cite journal | vauthors = Bergeron D, Poliquin L, Kozak CA, Rassart E | title = Identification of a common viral integration region in Cas-Br-E murine leukemia virus-induced non-T-, non-B-cell lymphomas | journal = Journal of Virology | volume = 65 | issue = 1 | pages = 7–15 | date = January 1991 | pmid = 1845910 | pmc = 240483 | doi = 10.1128/JVI.65.1.7-15.1991}}
• {{cite journal | vauthors = Bhagirath T, Abe S, Nojima T, Yoshida MC | title = Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma | journal = Genes, Chromosomes & Cancer | volume = 13 | issue = 2 | pages = 126–32 | date = June 1995 | pmid = 7542907 | doi = 10.1002/gcc.2870130209 | s2cid = 36929552 }}
• {{cite journal | vauthors = Liang H, Mao X, Olejniczak ET, Nettesheim DG, Yu L, Meadows RP, Thompson CB, Fesik SW | display-authors = 6 | title = Solution structure of the ets domain of Fli-1 when bound to DNA | journal = Nature Structural Biology | volume = 1 | issue = 12 | pages = 871–5 | date = December 1994 | pmid = 7773776 | doi = 10.1038/nsb1294-871 | s2cid = 26261743 }}
• {{cite journal | vauthors = May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Lunsford LB, Hromas R, Denny CT | display-authors = 6 | title = 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 | journal = Molecular and Cellular Biology | volume = 13 | issue = 12 | pages = 7393–8 | date = December 1993 | pmid = 8246959 | pmc = 364810 | doi = 10.1128/mcb.13.12.7393 }}
• {{cite journal | vauthors = Hromas R, May W, Denny C, Raskind W, Moore J, Maki RA, Beck E, Klemsz MJ | display-authors = 6 | title = Human FLI-1 localizes to chromosome 11Q24 and has an aberrant transcript in neuroepithelioma | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1172 | issue = 1–2 | pages = 155–8 | date = February 1993 | pmid = 8439553 | doi = 10.1016/0167-4781(93)90283-J }}
• {{cite journal | vauthors = Magnaghi-Jaulin L, Masutani H, Robin P, Lipinski M, Harel-Bellan A | title = SRE elements are binding sites for the fusion protein EWS-FLI-1 | journal = Nucleic Acids Research | volume = 24 | issue = 6 | pages = 1052–8 | date = March 1996 | pmid = 8604338 | pmc = 145748 | doi = 10.1093/nar/24.6.1052 }}
• {{cite journal | vauthors = Barbeau B, Bergeron D, Beaulieu M, Nadjem Z, Rassart E | title = Characterization of the human and mouse Fli-1 promoter regions | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1307 | issue = 2 | pages = 220–32 | date = June 1996 | pmid = 8679708 | doi = 10.1016/0167-4781(96)00060-7 }}
• {{cite journal | vauthors = Watson DK, Robinson L, Hodge DR, Kola I, Papas TS, Seth A | title = 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 | journal = Oncogene | volume = 14 | issue = 2 | pages = 213–21 | date = January 1997 | pmid = 9010223 | doi = 10.1038/sj.onc.1200839 | doi-access = free }}
• {{cite journal | vauthors = Kwiatkowski BA, Bastian LS, Bauer TR, Tsai S, Zielinska-Kwiatkowska AG, Hickstein DD | title = The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity | journal = The Journal of Biological Chemistry | volume = 273 | issue = 28 | pages = 17525–30 | date = July 1998 | pmid = 9651344 | doi = 10.1074/jbc.273.28.17525 | doi-access = free }}
• {{cite journal | vauthors = Carrère S, Verger A, Flourens A, Stehelin D, Duterque-Coquillaud M | title = Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains | journal = Oncogene | volume = 16 | issue = 25 | pages = 3261–8 | date = June 1998 | pmid = 9681824 | doi = 10.1038/sj.onc.1201868 | s2cid = 26807714 | doi-access = }}
• {{cite journal | vauthors = Zucman-Rossi J, Legoix P, Victor JM, Lopez B, Thomas G | title = Chromosome translocation based on illegitimate recombination in human tumors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 20 | pages = 11786–91 | date = September 1998 | pmid = 9751743 | pmc = 21718 | doi = 10.1073/pnas.95.20.11786 | bibcode = 1998PNAS...9511786Z | doi-access = free }}
• {{cite journal | vauthors = Dalgleish P, Sharrocks AD | title = The mechanism of complex formation between Fli-1 and SRF transcription factors | journal = Nucleic Acids Research | volume = 28 | issue = 2 | pages = 560–9 | date = January 2000 | pmid = 10606656 | pmc = 102515 | doi = 10.1093/nar/28.2.560 }}
• {{cite journal | vauthors = Knoop LL, Baker SJ | title = The splicing factor U1C represses EWS/FLI-mediated transactivation | journal = The Journal of Biological Chemistry | volume = 275 | issue = 32 | pages = 24865–71 | date = August 2000 | pmid = 10827180 | doi = 10.1074/jbc.M001661200 | doi-access = free }}
• {{cite journal | vauthors = Spyropoulos DD, Pharr PN, Lavenburg KR, Jackers P, Papas TS, Ogawa M, Watson DK | title = Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor | journal = Molecular and Cellular Biology | volume = 20 | issue = 15 | pages = 5643–52 | date = August 2000 | pmid = 10891501 | pmc = 86032 | doi = 10.1128/MCB.20.15.5643-5652.2000 }}
• {{cite journal | vauthors = Mastrangelo T, Modena P, Tornielli S, Bullrich F, Testi MA, Mezzelani A, Radice P, Azzarelli A, Pilotti S, Croce CM, Pierotti MA, Sozzi G | display-authors = 6 | title = A novel zinc finger gene is fused to EWS in small round cell tumor | journal = Oncogene | volume = 19 | issue = 33 | pages = 3799–804 | date = August 2000 | pmid = 10949935 | doi = 10.1038/sj.onc.1203762 | s2cid = 24580332 | doi-access = }}

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• {{MeshName|FLI1+protein,+human}}

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{{Transcription factors|g3}}

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Category:Transcription factors