FLI1
Encyclopedia
Friend leukemia integration 1 transcription factor (FLI1), also known as proto-oncogene Fli-1 or transcription factor ERGB, is a protein
that in humans is encoded by the human FLI1 gene
.
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.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the human FLI1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Fli-1 is a member of the ETS transcription factor familyETS transcription factor family
In the field of molecular biology, the ETS family is one of the largest families of transcription factors and is unique to metazoans. There are 29 genes in humans, 28 in the mouse, 10 in Caenorhabditis elegans and 9 in Drosophila. The founding member of this family was identified as a gene...
that was first identified in erythroleukemias induced by Friend Murine Leukemia Virus (F-MuLV
Friend virus
The Friend virus is a strain of murine leukemia virus identified by Charlotte Friend in 1956. The virus infects adult immunocompetent mice and is a well-established model for studying genetic resistance to infection by an immunosuppressive retrovirus. The Friend virus has been used for both...
). Fli-1 is activated through retroviral
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
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
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
/Epo-R
Erythropoietin receptor
The erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...
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. 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 TelETV6
ETV6 is an oncogene.-Interactions:ETV6 has been shown to interact with Grb2, FLI1 and HTATIP.-See also:* TEL-JAK2Mouse Mutant Alleles for Etv6 Marker Symbol for Mouse Gene. This symbol is assigned to the genomic locus by the...
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
Paris-Trousseau syndrome
Paris-Trousseau syndrome is an inherited disorder characterized by mild hemorrhagic tendency associated with 11q chromosome deletion.FLI1 has been suggested as a candidate....
has been suggested.