title: A small peptide derived from p53 linker region can resume the apoptotic activity of p53 by sequestering iASPP with p53.
abstract: One of the most important tumor suppression functions of p53 is its ability to induce apoptosis. iASPP is an inhibitory member of the ASPP protein family. It can specifically inhibit the normal function of p53 as a suppressor. The mechanism of iASPP suppressing the cell apoptotosis is through inhibiting the transactivation function of p53 on the promoters of proapoptotic genes by binding with p53. Therefore, relieving the combination of iASPP with p53 and leaving p53 free may be a useful strategy to activate p53 function. We therefore use A34, a small peptide derived from p53 linker region, to investigate the possibility of resuming the apoptosis activity of p53 by sequestering iASPP with p53 and derepressing p53. The results show that A34 can competitively combine with iASPP and therefore release p53 from iASPP; A34 can enhance the transcriptional activity of p53 on the promoters of Bax and PUMA; A34 can increase cell apoptosis and slow tumor growth in vitro and vivo. This study will open the way for using small molecule peptides that directly disturb the interaction of p53 with iASPP, thereby resume function of p53 as a suppressor.
authors.affiliation: Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; School of Rehabilitation Sciences, Seirei Christopher University, Hamamatsu, 433-8558, Japan.
authors.forename: Shou-Zhi
authors.initials: SZ
authors.lastname: Gu
authors.affiliation: Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zejunliu2000@aliyun.com.
authors.forename: Ze-Jun
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D010446:Peptide Fragments; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: A34; Apoptosis; Derepress; iASPP; p53