Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Binding Sites
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Core Binding Factor Alpha 2 Subunit
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Core Binding Factor alpha Subunits
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics*
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DNA-Binding Proteins / metabolism
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Histone Deacetylases
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Leukemia, Myeloid / genetics*
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Neoplasm Proteins*
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Proteins*
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Repressor Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
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Transcription Factors / metabolism*
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Translocation, Genetic*
Substances
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Core Binding Factor Alpha 2 Subunit
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Core Binding Factor alpha Subunits
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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SIN3 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Histone Deacetylases