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 Citations (Scopus)

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
Externally publishedYes

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Co-Repressor Proteins
Genetic Translocation
Acute Myeloid Leukemia
Leukemia
Transcription
Core Binding Factor Alpha 2 Subunit
Fusion reactions
Genes
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. / Lutterbach, Bart; Westendorf, Jennifer J; Linggi, Bryan; Isaac, Stuart; Seto, Edward; Hiebert, Scott W.

In: Journal of Biological Chemistry, Vol. 275, No. 1, 07.01.2000, p. 651-656.

Research output: Contribution to journalArticle

Lutterbach, Bart ; Westendorf, Jennifer J ; Linggi, Bryan ; Isaac, Stuart ; Seto, Edward ; Hiebert, Scott W. / A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 1. pp. 651-656.
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