Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the FLI1gene, which is a proto-oncogene.[5][6][7]
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 retroviralinsertional 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.[8] with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with enhancer-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 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]
^"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. ISBN 978-1-4020-4966-8. 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.