FLI1

FLI1
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 1FLI,1X66,2YTU,5E8G,5E8I
Identifiers
Aliases	FLI1,EWSR2, SIC-1, Fli-1 proto-oncogene, ETS transcription factor, BDPLT21, FLI-1
External IDs	OMIM:193067;MGI:95554;HomoloGene:55624;GeneCards:FLI1;OMA:FLI1 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q24.3 Start 128,686,535bp End 128,813,267bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 A4|9 17.74 cM Start 32,333,500bp End 32,454,157bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in monocyte granulocyte blood spleen bone marrow cells trabecular bone appendix lymph node right lung upper lobe of left lung Top expressed in dermis tibiofemoral joint spleen left lung lobe mesenteric lymph nodes granulocyte blood genital tubercle abdominal wall stroma of bone marrow More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding RNA polymerase II cis-regulatory region sequence-specific DNA binding chromatin binding sequence-specific DNA binding DNA-binding transcription factor activity DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus cytosol nuclear body Biological process megakaryocyte development positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II hemostasis regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II cell differentiation animal organ morphogenesis blood circulation transcription, DNA-templated positive regulation of transcription, DNA-templated Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 2313 14247 Ensembl ENSG00000151702 ENSMUSG00000016087 UniProt Q01543 P26323 RefSeq (mRNA) NM_001167681 NM_001271010 NM_001271012 NM_002017 NM_008026 RefSeq (protein) NP_001161153 NP_001257939 NP_001257941 NP_002008 NP_001161153.1 NP_032052 Location (UCSC) Chr 11: 128.69 – 128.81 Mb Chr 9: 32.33 – 32.45 Mb PubMedsearch
Wikidata
View/Edit Human View/Edit Mouse

Friend leukemia integration 1 transcription factor(FLI1), also known astranscription factor ERGB,is aproteinthat in humans is encoded by theFLI1gene,which is aproto-oncogene.

Function

Fli-1 is a member of theETS transcription factor familythat was first identified inerythroleukemiasinduced by Friend Murine Leukemia Virus (F-MuLV). Fli-1 is activated throughretroviralinsertional mutagenesisin 90% of F-MuLV-induced erythroleukemias. The constitutive activation of fli-1 inerythroblastsleads to a dramatic shift in theEpo/Epo-Rsignal transduction pathway, blocking erythroid differentiation, activating theRaspathway, 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.

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 pediatricEwing’s sarcomaa chromosomal translocation generates a fusion of the 5’ transactivation domain ofEWSR1(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.with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction withenhancer-like GGAA-microsatellites.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 theTeltranscription 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.

A possible association withParis-Trousseau syndromehas been suggested.

Further reading

• Ben-David Y, Giddens EB, Bernstein A (February 1990)."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.Bibcode:1990PNAS...87.1332B.doi:10.1073/pnas.87.4.1332.PMC53469.PMID2304901.
• Ben-David Y, Giddens EB, Letwin K, Bernstein A (June 1991)."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.doi:10.1101/gad.5.6.908.PMID2044959.
• Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, et al. (September 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours".Nature.359(6391): 162–5.Bibcode:1992Natur.359..162D.doi:10.1038/359162a0.PMID1522903.S2CID4331584.
• Pereira R, Quang CT, Lesault I, Dolznig H, Beug H, Ghysdael J (February 1999). "FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts".Oncogene.18(8): 1597–608.doi:10.1038/sj.onc.1202534.PMID10102630.S2CID25190024.
• Tamir A, Howard J, Higgins RR, Li YJ, Berger L, Zacksenhaus E, et al. (June 1999)."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.doi:10.1128/mcb.19.6.4452.PMC104404.PMID10330185.
• Zochodne B, Truong AH, Stetler K, Higgins RR, Howard J, Dumont D, et al. (May 2000). "Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia".Oncogene.19(19): 2296–304.doi:10.1038/sj.onc.1203590.PMID10822380.S2CID7468572.
• Starck J, Doubeikovski A, Sarrazin S, Gonnet C, Rao G, Skoultchi A, et al. (January 1999)."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.doi:10.1128/mcb.19.1.121.PMC83871.PMID9858537.
• Truong AH, Ben-David Y (December 2000). "The role of Fli-1 in normal cell function and malignant transformation".Oncogene.19(55): 6482–9.doi:10.1038/sj.onc.1204042.PMID11175364.S2CID28146474.
• Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator".Cancer Research.53(24): 5859–63.PMID7503813.
• Dhulipala PD, Lee L, Rao VN, Reddy ES (September 1998)."Fli-1b is generated by usage of differential splicing and alternative promoter".Oncogene.17(9): 1149–57.doi:10.1038/sj.onc.1202030.PMID9764825.
• Rao VN, Ohno T, Prasad DD, Bhattacharya G, Reddy ES (August 1993). "Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein".Oncogene.8(8): 2167–73.PMID8336942.
• Ban J, Siligan C, Kreppel M, Aryee D, Kovar H (2006). "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. Vol. 587. pp. 41–52.doi:10.1007/978-1-4020-5133-3_4.ISBN978-1-4020-4966-8.PMID17163154.
• Prasad DD, Rao VN, Reddy ES (October 1992). "Structure and expression of human Fli-1 gene".Cancer Research.52(20): 5833–7.PMID1394211.
• Watson DK, Smyth FE, Thompson DM, Cheng JQ, Testa JR, Papas TS, Seth A (October 1992). "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.PMID1445800.
• Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, et al. (September 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours".Nature.359(6391): 162–5.Bibcode:1992Natur.359..162D.doi:10.1038/359162a0.PMID1522903.S2CID4331584.
• Baud V, Lipinski M, Rassart E, Poliquin L, Bergeron D (September 1991). "The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24".Genomics.11(1): 223–4.doi:10.1016/0888-7543(91)90124-W.PMID1765382.
• Bergeron D, Poliquin L, Kozak CA, Rassart E (January 1991)."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.doi:10.1128/JVI.65.1.7-15.1991.PMC240483.PMID1845910.
• Bhagirath T, Abe S, Nojima T, Yoshida MC (June 1995). "Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma".Genes, Chromosomes & Cancer.13(2): 126–32.doi:10.1002/gcc.2870130209.PMID7542907.S2CID36929552.
• Liang H, Mao X, Olejniczak ET, Nettesheim DG, Yu L, Meadows RP, et al. (December 1994). "Solution structure of the ets domain of Fli-1 when bound to DNA".Nature Structural Biology.1(12): 871–5.doi:10.1038/nsb1294-871.PMID7773776.S2CID26261743.
• May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Lunsford LB, et al. (December 1993)."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.doi:10.1128/mcb.13.12.7393.PMC364810.PMID8246959.
• Hromas R, May W, Denny C, Raskind W, Moore J, Maki RA, et al. (February 1993). "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.doi:10.1016/0167-4781(93)90283-J.PMID8439553.
• Magnaghi-Jaulin L, Masutani H, Robin P, Lipinski M, Harel-Bellan A (March 1996)."SRE elements are binding sites for the fusion protein EWS-FLI-1".Nucleic Acids Research.24(6): 1052–8.doi:10.1093/nar/24.6.1052.PMC145748.PMID8604338.
• Barbeau B, Bergeron D, Beaulieu M, Nadjem Z, Rassart E (June 1996). "Characterization of the human and mouse Fli-1 promoter regions".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.1307(2): 220–32.doi:10.1016/0167-4781(96)00060-7.PMID8679708.
• Watson DK, Robinson L, Hodge DR, Kola I, Papas TS, Seth A (January 1997)."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.doi:10.1038/sj.onc.1200839.PMID9010223.
• Kwiatkowski BA, Bastian LS, Bauer TR, Tsai S, Zielinska-Kwiatkowska AG, Hickstein DD (July 1998)."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.doi:10.1074/jbc.273.28.17525.PMID9651344.
• Carrère S, Verger A, Flourens A, Stehelin D, Duterque-Coquillaud M (June 1998). "Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains".Oncogene.16(25): 3261–8.doi:10.1038/sj.onc.1201868.PMID9681824.S2CID26807714.
• Zucman-Rossi J, Legoix P, Victor JM, Lopez B, Thomas G (September 1998)."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.Bibcode:1998PNAS...9511786Z.doi:10.1073/pnas.95.20.11786.PMC21718.PMID9751743.
• Dalgleish P, Sharrocks AD (January 2000)."The mechanism of complex formation between Fli-1 and SRF transcription factors".Nucleic Acids Research.28(2): 560–9.doi:10.1093/nar/28.2.560.PMC102515.PMID10606656.
• Knoop LL, Baker SJ (August 2000)."The splicing factor U1C represses EWS/FLI-mediated transactivation".The Journal of Biological Chemistry.275(32): 24865–71.doi:10.1074/jbc.M001661200.PMID10827180.
• Spyropoulos DD, Pharr PN, Lavenburg KR, Jackers P, Papas TS, Ogawa M, Watson DK (August 2000)."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.doi:10.1128/MCB.20.15.5643-5652.2000.PMC86032.PMID10891501.
• Mastrangelo T, Modena P, Tornielli S, Bullrich F, Testi MA, Mezzelani A, et al. (August 2000). "A novel zinc finger gene is fused to EWS in small round cell tumor".Oncogene.19(33): 3799–804.doi:10.1038/sj.onc.1203762.PMID10949935.S2CID24580332.

External links

• FLI1+protein,+humanat the U.S. National Library of MedicineMedical Subject Headings(MeSH)

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.