Biology:FLI1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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

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.[4] with strong transforming capabilities. EWS/Fli-1 may steer clinically important genes via interaction with enhancer-like GGAA-microsatellites.[5] 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.[6]

References

  1. ↑ "The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24". Genomics 11 (1): 223–4. September 1991. doi:10.1016/0888-7543(91)90124-W. PMID 1765382. 
  2. ↑ "Structure and expression of human Fli-1 gene". Cancer Research 52 (20): 5833–7. October 1992. PMID 1394211. 
  3. ↑ "Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein". Oncogene 8 (8): 2167–73. August 1993. PMID 8336942. 
  4. ↑ "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Research 53 (24): 5859–63. December 1993. PMID 7503813. 
  5. ↑ Musa, Julian et al. (2018-12-27). "Cooperation of dominant oncogenes with regulatory germline variants shapes clinical outcomes in childhood cancer" (in en). bioRxiv: 506659. doi:10.1101/506659. https://www.biorxiv.org/content/early/2018/12/27/506659. 
  6. ↑ "FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia". The Journal of Clinical Investigation 114 (1): 77–84. July 2004. doi:10.1172/JCI21197. PMID 15232614. 

Further reading

External links

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



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