Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''FLI1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
, which is a
proto-oncogene.
Function
Fli-1 is a member of the
ETS transcription factor family
In the field of molecular biology, the ETS (E26 transformation-specific or E-twenty-six. (Erythroblast Transformation Specific)) family is one of the largest families of transcription factors and is unique to animals. There are 29 genes in human ...
that was first identified in
erythroleukemias induced by Friend Murine Leukemia Virus (
F-MuLV). Fli-1 is activated through
retroviral
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...
insertional mutagenesis In molecular biology, insertional mutagenesis is the creation of mutations of DNA by addition of one or more base pairs. Such insertional mutations can occur naturally, mediated by viruses or transposons, or can be artificially created for research ...
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
Ras or RAS may refer to:
Arts and media
* RAS Records Real Authentic Sound, a reggae record label
* Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service
* Rás 1, an Icelandic radio station
* Rás 2, an Icelandic radio sta ...
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
Ewing sarcoma is a type of cancer that forms in bone or soft tissue. Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. The most common areas where it begins are the legs, pelvis, and chest wall. In abou ...
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.
with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with
enhnacer-like GGAA-microsatellites.
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.
References
Further reading
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External links
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{{DEFAULTSORT:Fli1
Transcription factors