Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein.

The AML1-CBF beta 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 translocations. 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 well 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 role in cell differentiation. On the other hand, the MOZ-CBP fusion protein, which is created by the t(8;16) translocation associated with acute monocytic leukemia, inhibits AML1-mediated transcription and differentiation of M1 cells. These results suggest that MOZ-CBP might induce leukemia by antagonizing the function of the AML1 complex.
Mesh Terms:
Acetyltransferases, Amino Acid Sequence, Base Sequence, CREB-Binding Protein, Cell Differentiation, Cell Line, Core Binding Factor Alpha 2 Subunit, DNA Primers, DNA-Binding Proteins, Histone Acetyltransferases, Humans, Macrophages, Molecular Sequence Data, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Transcriptional Activation
EMBO J.
Date: Dec. 17, 2001
Download Curated Data For This Publication
111832
Switch View:
  • Interactions 7