Association of MTG8 (ETO/CDR), a leukemia-related protein, with serine/threonine protein kinases and heat shock protein HSP90 in human hematopoietic cell lines.

Abstract	A proto-oncogene, MTG8 (ETO/CDR), is disrupted in the t(8;21) translocation associated with acute myeloid leukemia, and the gene product, MTG8, is a phosphoprotein capable of cell transformation in concert with v-H-ras. To obtain insight into functional regulation of MTG8 by phosphorylation, we studied protein kinases that interact with, and phosphorylate, MTG8 in vitro. Recombinant MTG8 protein was first found to be associated with two serine/threonine protein kinases in cell extracts from both HEL cells and a leukemic cell line carrying t(8;21). A cytoplasmic protein kinase of 61 kDa (MTG8N-kinase) phosphorylated the amino-terminal of MTG8, and another of 52 kDa (MTG8C-kinase) phosphorylated the carboxyl-terminal domain. In addition, we demonstrated that heat shock protein 90 (HSP90) specifically binds to the amino-terminal domain of MTG8 in vitro and in vivo. Thus, our results shed new light on post-translational regulation of MTG8, perturbation of which, in AML1-MTG8 protein, probably contributes to leukemogenesis.
Authors	A Komori, E Sueoka, H Fujiki, M Ishii, T Kozu
Journal	Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 90 Issue 1 Pg. 60-8 (Jan 1999) ISSN: 0910-5050 [Print] Japan
PMID	10076566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins HSP90 Heat-Shock Proteins MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins RUNX1 Translocation Partner 1 Protein RUNX1T1 protein, human Recombinant Fusion Proteins Transcription Factors Protein Serine-Threonine Kinases
Topics	Acute Disease Blotting, Western Cell Line DNA-Binding Proteins (genetics, isolation & purification, metabolism) Electrophoresis, Polyacrylamide Gel HL-60 Cells HSP90 Heat-Shock Proteins (isolation & purification, metabolism) Hematopoietic Stem Cells Humans Leukemia, Myeloid (genetics) Leukemia, Promyelocytic, Acute Polymerase Chain Reaction Protein Binding Protein Serine-Threonine Kinases (isolation & purification, metabolism) Proto-Oncogene Mas Proto-Oncogene Proteins Proto-Oncogenes RUNX1 Translocation Partner 1 Protein Recombinant Fusion Proteins (isolation & purification, metabolism) Transcription Factors (genetics, isolation & purification, metabolism)

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