FLI1

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FLI1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFLI1, EWSR2, SIC-1, Fli-1 proto-oncogene, ETS transcription factor, BDPLT21, FLI-1
External IDsOMIM: 193067 MGI: 95554 HomoloGene: 55624 GeneCards: FLI1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 9: 32.33 – 32.45 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[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 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.[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]

A possible association with Paris-Trousseau syndrome has been suggested.[10]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151702 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016087 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. PMID 1765382.
  6. ^ Prasad DD, Rao VN, Reddy ES (October 1992). "Structure and expression of human Fli-1 gene". Cancer Research. 52 (20): 5833–7. PMID 1394211.
  7. ^ 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. PMID 8336942.
  8. ^ Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Research. 53 (24): 5859–63. PMID 7503813.
  9. ^ Musa J, Cidre-Aranaz F, Aynaud M, Orth M, Mirabeau O, Varon M, Grossetete S, Surdez D, et al. (2018-12-27). "Cooperation of dominant oncogenes with regulatory germline variants shapes clinical outcomes in childhood cancer". bioRxiv: 506659. doi:10.1101/506659.
  10. ^ Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, et al. (July 2004). "FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia". The Journal of Clinical Investigation. 114 (1): 77–84. doi:10.1172/JCI21197. PMC 437972. PMID 15232614.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.