The Notch Regulator MAML1 Interacts with p53 and Functions as a Coactivator

摘要: Members of the evolutionarily conserved Mastermind (MAM) protein family, including three related mammalian Mastermind-like (MAML) proteins MAML1–3, function as crucial coactivators Notch-mediated transcriptional activation. Given recent evidence cross-talk between p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a coactivator p53. Indeed, show here that is able to interact with We MAML1-p53 interaction involves N-terminal region DNA-binding domain p53, use chromatin immunoprecipitation assay part activator complex binds native p53-response elements within promoter target genes. Overexpression wild-type well mutant, defective in signaling, enhanced p53-dependent gene induction cells, whereas knockdown reduced expression. increases half-life enhances its phosphorylation/acetylation upon DNA damage cells. Finally, RNA interference-mediated single Caenorhabditis elegans MAML homolog, Lag-3, led substantial abrogation p53-mediated germ-cell apoptotic response markedly expression Ced-13 Egl-1, downstream pro-apoptotic targets C. homolog Cep-1. Thus, present for novel independent signaling pathway.