A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia.

Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW
J Biol Chem. 2000 275 (1): 651-6

PMID: 10617663 · DOI:10.1074/jbc.275.1.651

AML1 is one of the most frequently translocated genes in human leukemia. Here we demonstrate that acute myeloid leukemia-1 (AML-1) (Runx-1) represses transcription from a native promoter, p21(Waf1/Cip1). Unexpectedly, this repression did not require interactions with the Groucho co-repressor. To define the mechanism of repression, we asked whether other co-repressors could interact with AML-1. We demonstrate that AML-1 interacts with the mSin3 co-repressors. Moreover, endogenous AML-1 associated with endogenous mSin3A in mammalian cells. A deletion mutant of AML-1 that did not interact with mSin3A failed to repress transcription. The AML-1/mSin3 association suggests a mechanism of repression for the chromosomal translocation fusion proteins that disrupt AML-1.

MeSH Terms (17)

Acute Disease Binding Sites Core Binding Factor Alpha 2 Subunit Core Binding Factor alpha Subunits Cyclin-Dependent Kinase Inhibitor p21 Cyclins DNA-Binding Proteins Histone Deacetylases Leukemia, Myeloid Neoplasm Proteins Protein Binding Protein Structure, Tertiary Proto-Oncogene Proteins Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Translocation, Genetic

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