title: iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes.
abstract: The ability to induce apoptosis is the most important tumor-suppression function of p53. Inhibitory member of apoptosis-stimulating protein of p53 family (iASPP) is an apoptotic-specific regulator of p53. iASPP suppresses apoptosis by inhibiting the transactivation function of p53 on the promoters of proapoptotic genes; however, the mechanism whereby iASPP influences apoptosis in tumor cells with mutant or deficient p53 has not been completely defined. In this study, we investigated the role of iASPP in the p63/p73 apoptosis pathway. iASPP inhibited apoptosis independently of p53 in tumor cells, mainly by inhibiting the transcriptional activity of p63/p73 on the promoters of proapoptotic genes. Because p63 and p73 are rarely mutated in human cancers, inhibiting the expression of endogenous iASPP may provide a useful strategy for restoring the apoptotic activity of p63 and p73 in human tumors with p53 loss or mutation. These results represent a promising new strategy for the treatment of cancers with non-wild-type p53.
authors.affiliation: Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.forename: Shou-Zhi
authors.initials: SZ
authors.lastname: Gu
authors.forename: Ze-Jun
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; C495901:TP53 protein, human; C115051:TP63 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins