FLI1

Last updated
FLI1
Protein FLI1 PDB 1fli.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FLI1 , EWSR2, SIC-1, Fli-1 proto-oncogene, ETS transcription factor, BDPLT21, FLI-1
External IDs OMIM: 193067; MGI: 95554; HomoloGene: 55624; GeneCards: FLI1; OMA:FLI1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

Contents

NP_032052

Location (UCSC) Chr 11: 128.69 – 128.81 Mb Chr 9: 32.33 – 32.45 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

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. [ citation needed ]

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 enhancer-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.[ citation needed ]

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

Related Research Articles

<span class="mw-page-title-main">Ewing sarcoma</span> Type of cancer

Ewing sarcoma is a type of pediatric 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 about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis. Complications may include a pleural effusion or paraplegia.

<span class="mw-page-title-main">ETV6</span> Protein-coding gene in the species Homo sapiens

ETV6 protein is a transcription factor that in humans is encoded by the ETV6 gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. However, its gene, ETV6 frequently suffers various mutations that lead to an array of potentially lethal cancers, i.e., ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or progression of certain cancers. However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers.

<span class="mw-page-title-main">MN1 (gene)</span> Protein-coding gene in the species Homo sapiens

MN1 is a gene found on human chromosome 22, with gene map locus 22q12.3-qter. Its official full name is meningioma 1 because it is disrupted by a balanced translocation (4;22) in a meningioma.

<span class="mw-page-title-main">ETS1</span> Protein-coding gene in the species Homo sapiens

Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. The protein encoded by this gene belongs to the ETS family of transcription factors.

<span class="mw-page-title-main">ELK1</span> Protein-coding gene in humans

ETS Like-1 protein Elk-1 is a protein that in humans is encoded by the ELK1. Elk-1 functions as a transcription activator. It is classified as a ternary complex factor (TCF), a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences. Elk1 plays important roles in various contexts, including long-term memory formation, drug addiction, Alzheimer's disease, Down syndrome, breast cancer, and depression.

<span class="mw-page-title-main">ATF1</span> Protein-coding gene in humans

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

<span class="mw-page-title-main">ETS2</span> Protein-coding gene in humans

Protein C-ETS2 is a protein that in humans is encoded by the ETS2 gene. The protein encoded by this gene belongs to the ETS family of transcription factors. It has been found to play a key role in the development of inflammatory bowel disease.

<span class="mw-page-title-main">ETV4</span> Protein-coding gene in the species Homo sapiens

ETS translocation variant 4 (ETV4), also known as polyoma enhancer activator 3 (PEA3), is a member of the PEA3 subfamily of Ets transcription factors.

<span class="mw-page-title-main">LMO2</span> Protein-coding gene in the species Homo sapiens

LIM domain only 2, also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2 gene.

<span class="mw-page-title-main">SPI1</span> Protein-coding gene in the species Homo sapiens

Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene.

<span class="mw-page-title-main">RNA-binding protein EWS</span> Human protein and coding gene

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. It is one of 3 proteins in the FET protein family.

<i>ERG</i> (gene) Protein-coding gene in the species Homo sapiens

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

<span class="mw-page-title-main">RNA-binding protein FUS</span> Human protein and coding gene

RNA-binding protein FUS/TLS, also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the FUS gene.

<span class="mw-page-title-main">ETV1</span> Protein-coding gene in the species Homo sapiens

ETS translocation variant 1 is a protein that in humans is encoded by the ETV1 gene.

<span class="mw-page-title-main">TLX1</span> Protein coding gene in Humans

T-cell leukemia homeobox protein 1 is a protein that in humans is encoded by the TLX1 gene, which was initially named HOX11.

<span class="mw-page-title-main">ELK4</span> Protein-coding gene in the species Homo sapiens

ETS domain-containing protein Elk-4 is a protein that in humans is encoded by the ELK4 gene.

<span class="mw-page-title-main">LYL1</span> Protein-coding gene in the species Homo sapiens

Protein lyl-1 is a protein that in humans is encoded by the LYL1 gene.

<span class="mw-page-title-main">ETS transcription factor family</span> Protein family

In the field of molecular biology, the ETSfamily is one of the largest families of transcription factors and is unique to animals. 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 transduced by the leukemia virus, E26. The members of the family have been implicated in the development of different tissues as well as cancer progression.

SAP1A is one of a family of proteins that contains a unique DNA binding domain termed the ETS domain.

EWS/FLI1 is an oncogenic protein that is pathognomonic for Ewing sarcoma. It is found in approximately 90% of all Ewing sarcoma tumors with the remaining 10% of fusions substituting one fusion partner with a closely related family member.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000151702 Ensembl, May 2017
  2. 1 2 3 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 J, Cidre-Aranaz F, Aynaud MM, Orth MF, Mirabeau O, Varon M, Grossetête S, Surdez D, Ohmura S, Gerke JS, Marchetto A (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.