FLI1

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]

FLI1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFLI1, EWSR2, SIC-1, Fli-1 proto-oncogene, ETS transcription factor, BDPLT21
External IDsOMIM: 193067 MGI: 95554 HomoloGene: 55624 GeneCards: FLI1
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q24.3Start128,686,535 bp[1]
End128,813,267 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 9: 32.42 – 32.54 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

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 enhnacer-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.

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

References

  1. GRCh38: Ensembl release 89: ENSG00000151702 - Ensembl, May 2017
  2. 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, Julian; Cidre-Aranaz, Florencia; Aynaud, Marie-Ming; Orth, Martin; Mirabeau, Olivier; Varon, Mor; Grossetete, Sandrine; Surdez, Didier; 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

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

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