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

Bart Lutterbach, Jennifer J. Westendorf, Bryan Linggi, Stuart Isaac, Edward Seto, Scott W. Hiebert

Research output: Contribution to journalArticle

211 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)651-656
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number1
DOIs
StatePublished - Jan 7 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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