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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rokudai, Susumu Taya, Yoichi Arnal, Suzzette M. Kitabayashi, Issay Laptenko, Oleg Prives, Carol |
| Description | Author Affiliation: Rokudai S ( Department of Biological Sciences, Columbia University, New York, NY 10027, USA.); |
| Abstract | Monocytic leukemia zinc finger (MOZ)/KAT6A is a MOZ, Ybf2/Sas3, Sas2, Tip60 (MYST)-type histone acetyltransferase that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and Ets family transcription factor PU.1-dependent transcription. We previously reported that MOZ directly interacts with p53 and is essential for p53-dependent selective regulation of p21 expression. We show here that MOZ is an acetyltransferase of p53 at K120 and K382 and colocalizes with p53 in promyelocytic leukemia (PML) nuclear bodies following cellular stress. The MOZ-PML-p53 interaction enhances MOZ-mediated acetylation of p53, and this ternary complex enhances p53-dependent p21 expression. Moreover, we identified an Akt/protein kinase B recognition sequence in the PML-binding domain of MOZ protein. Akt-mediated phosphorylation of MOZ at T369 has a negative effect on complex formation between PML and MOZ. As a result of PML-mediated suppression of Akt, the increased PML-MOZ interaction enhances p21 expression and induces p53-dependent premature senescence upon forced PML expression. Our research demonstrates that MOZ controls p53 acetylation and transcriptional activity via association with PML. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 10 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Histone Acetyltransferases Metabolism Leukemia, Promyelocytic, Acute Tumor Suppressor Protein P53 Acetylation Animals Cell Aging Cells, Cultured Cyclin-Dependent Kinase Inhibitor P21 Gene Knockout Techniques Antagonists & Inhibitors Chemistry Deficiency Genetics Intranuclear Inclusion Bodies Mice Models, Biological Multiprotein Complexes Proto-Oncogene Proteins C-akt RNA, Small Interfering Recombinant Proteins P300-CBP Transcription Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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