TY - JOUR
T1 - A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia
AU - Lutterbach, Bart
AU - Westendorf, Jennifer J.
AU - Linggi, Bryan
AU - Isaac, Stuart
AU - Seto, Edward
AU - Hiebert, Scott W.
PY - 2000/1/7
Y1 - 2000/1/7
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.275.1.651
DO - 10.1074/jbc.275.1.651
M3 - Article
C2 - 10617663
AN - SCOPUS:0034614382
SN - 0021-9258
VL - 275
SP - 651
EP - 656
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -