Oligomerization of the ABL Tyrosine Kinase by the Ets Protein TEL in Human Leukemia
Open Access
- 1 August 1996
- journal article
- case report
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 16 (8), 4107-4116
- https://doi.org/10.1128/mcb.16.8.4107
Abstract
TEL is a member of the Ets family of transcription factors which are frequently rearranged in human leukemia. The mechanism of TEL-mediated transformation, however, is unknown. We report the cloning and characterization of a chromosomal translocation associated with acute myeloid leukemia which fuses TEL to the ABL tyrosine kinase. The TEL-ABL fusion confers growth factor-independent growth to the marine hematopoietic cell line Ba/F3 and transforms Rat-1 fibroblasts and primary murine bone marrow cells. TEL-ABL is constitutively tyrosine phosphorylated and localizes to the cytoskeleton. A TEL-ABL mutant containing an ABL kinase-inactivating mutation is not constitutively phosphorylated and is nontransforming but retains cytoskeletal localization. However, constitutive phosphorylation, cytoskeletal localization, and transformation are all dependent upon a highly conserved region of TEL termed the helix-loop-helix (HLH) domain. TEL-ABL formed HLH-dependent homo-oligomers in vitro, a process critical for tyrosine kinase activation. These experiments suggest that oligomerization of TEL-ABL mediated by the TEL HLH domain is required for tyrosine kinase activation, cytoskeletal localization, and transformation. These data also suggest that oligomerization of Ets proteins through the highly conserved HLH domain may represent a previously unrecognized phenomenon.Keywords
This publication has 57 references indexed in Scilit:
- Alternative signals to RAS for hematopoietic transformation by the BCR-ABL oncogeneCell, 1995
- The activities of two Ets-related transcription factors required for drosophila eye development are modulated by the Ras/MAPK pathwayCell, 1994
- Differential Complementation of Bcr-Abl Point Mutants with c-MycScience, 1994
- Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocationCell, 1994
- The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity [published erratum appears in J Cell Biol 1994 Mar;124(5):865]The Journal of cell biology, 1994
- Fusion Between Transcription Factor CBFβ/PEBP2β and a Myosin Heavy Chain in Acute Myeloid LeukemiaScience, 1993
- Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cellsCancer Genetics and Cytogenetics, 1992
- Tyrosine Kinase Activity and Transformation Potency of bcr-abl Oncogene ProductsScience, 1990
- Fused transcript of abl and bcr genes in chronic myelogenous leukaemiaNature, 1985
- A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa StainingNature, 1973