FLI1

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Fli-1 proto-oncogene, ETS transcription factor
Protein FLI1 PDB 1fli.png
PDB rendering based on 1fli.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FLI1 ; EWSR2; SIC-1
External IDs OMIM193067 MGI95554 HomoloGene55624 GeneCards: FLI1 Gene
RNA expression pattern
PBB GE FLI1 210786 s at tn.png
PBB GE FLI1 204236 at tn.png
PBB GE FLI1 211825 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2313 14247
Ensembl ENSG00000151702 ENSMUSG00000016087
UniProt Q01543 P26323
RefSeq (mRNA) NM_001167681 NM_008026
RefSeq (protein) NP_001161153 NP_032052
Location (UCSC) Chr 11:
128.56 – 128.68 Mb
Chr 9:
32.42 – 32.54 Mb
PubMed search [1] [2]

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.[1][2][3]

Function[edit]

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[edit]

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 EWS with the 3’ Ets domain of Fli-1. The resulting fusion oncoprotein, EWS/Fli-1, acts as an aberrant transcriptional activator.[4] with strong transforming capabilities. 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.[5]

References[edit]

  1. ^ 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. 
  2. ^ Prasad DD, Rao VN, Reddy ES (October 1992). "Structure and expression of human Fli-1 gene". Cancer Research 52 (20): 5833–7. PMID 1394211. 
  3. ^ 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. 
  4. ^ Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Res. 53 (24): 5859–63. PMID 7503813. 
  5. ^ Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, Danos O, Albagli O, Vainchenker W, Favier R (July 2004). "FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia". J. Clin. Invest. 114 (1): 77–84. doi:10.1172/JCI21197. PMC 437972. PMID 15232614. 


Further reading[edit]

External links[edit]

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