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- Title
Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein.
- Authors
Kitabayashi, Issay; Aikawa, Vukiko; Nguyen, Lan Anh; Vokoyama, Akihiko; Ohki, Misao
- Abstract
The AML1-CBFβ transcription factor complex is the most frequent target of specific chromosome translocations in human leukemia. The MOZ gene, which encodes a histone acetyltransferase (HAT), is also involved in some leukemia-associated transtocations. We report here that MOZ is part of the AML1 complex and strongly stimulates AML1-mediated transcription. The stimulation of AML1-mediated transcription is independent of the inherent HAT activity of MOZ. Rather, a potent transactivation domain within MOZ appears to be essential for stimulation of AML1-mediated transcription. MOZ, as welt as CBP and MOZ-CBP, can acetylate AML1 in vitro. The amount of AML1-MOZ complex increases during the differentiation of M1 myeloid cells into monocytes/macrophages, suggesting that the AML1-MOZ complex might play a rote in cell differentiation. On the other hand, the MOZ-CBP fusion protein, which is created by the t(8;16) transtocation associated with acute monocytic leukemia, inhibits AML1-mediated transcription and differentiation of Ml1cells. These results suggest that MOZ-CBP might induce leukemia by antagonizing the function of the AML1 complex.
- Subjects
LEUKEMIA; MONOCYTES; ACETYLTRANSFERASES; CHROMOSOMAL translocation; ACTIVATION (Chemistry); CHROMOSOMES
- Publication
EMBO Journal, 2001, Vol 20, Issue 24, p7184
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/20.24.7184