FLI1

FLI1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1FLI, 1X66, 2YTU, 5E8G, 5E8I
Identifiers
Aliases	FLI1, EWSR2, SIC-1, Fli-1 proto-oncogene, ETS transcription factor
External IDs	MGI: 95554 HomoloGene: 55624 GeneCards: FLI1
Genetically Related Diseases
myopia[1]
Gene ontology Molecular function • protein binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • chromatin binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • RNA polymerase II distal enhancer sequence-specific DNA binding • DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Cellular component • nucleus Biological process • megakaryocyte development • positive regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • hemostasis • regulation of transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • cell differentiation • animal organ morphogenesis • blood circulation • transcription, DNA-templated Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2313	14247
Ensembl	ENSG00000151702	ENSMUSG00000016087
UniProt	Q01543	P26323
RefSeq (mRNA)	NM_001167681 NM_001271010 NM_001271012 NM_002017	NM_008026
RefSeq (protein)	NP_001161153.1 NP_001257939.1 NP_001257941.1 NP_002008.2 NP_001161153.1	NP_032052.1
Location (UCSC)	Chr 11: 128.69 – 128.81 Mb	Chr 9: 32.42 – 32.54 Mb
PubMed search	[2]	[3]
Wikidata

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.^[4][5][6]

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 EWS with the 3’ Ets domain of Fli-1. The resulting fusion oncoprotein, EWS/Fli-1, acts as an aberrant transcriptional activator.^[7] 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.

A possible association with Paris-Trousseau syndrome has been suggested.^[8]

References

Further reading

External links

• FLI1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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

PDB gallery
1fli: DNA-BINDING DOMAIN OF FLI-1  1x66: Solution structure of the SAM_PNT-domain of the human friend LEUKEMIAINTEGRATION 1 transcription factor