Friend leukemia integration 1 transcription factor (FLI1), also known astranscription factor ERGB, is aprotein that in humans is encoded by theFLI1gene, which is aproto-oncogene.[5][6][7]
Fli-1 is a member of theETS transcription factor family that was first identified inerythroleukemias induced by Friend Murine Leukemia Virus (F-MuLV). Fli-1 is activated throughretroviralinsertional mutagenesis in 90% of F-MuLV-induced erythroleukemias. The constitutive activation of fli-1 inerythroblasts leads to a dramatic shift in theEpo/Epo-R signal transduction pathway, blocking erythroid differentiation, activating theRas 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]
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 sarcoma a 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.[8] with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction withenhancer-like GGAA-microsatellites.[9] 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 theTel 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]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
^Prasad DD, Rao VN, Reddy ES (October 1992). "Structure and expression of human Fli-1 gene".Cancer Research.52 (20):5833–7.PMID1394211.
^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.
^Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator".Cancer Research.53 (24):5859–63.PMID7503813.
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.
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.
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.
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.
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.
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.
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.
