title: MOZ increases p53 acetylation and premature senescence through its complex formation with PML.
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.
authors: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors: Susumu
authors: S
authors: Rokudai
authors: Oleg
authors: O
authors: Laptenko
authors: Suzzette M
authors: SM
authors: Arnal
authors: Yoichi
authors: Y
authors: Taya
authors: Issay
authors: I
authors: Kitabayashi
authors: Carol
authors: C
authors: Prives
mesh_terms: D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D055786:Gene Knockout Techniques; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human; C511438:MOZ protein, mouse; D050880:p300-CBP Transcription Factors; D051057:Proto-Oncogene Proteins c-akt