title: Identification of prohibitin and prohibiton as novel factors binding to the p53 induced gene 3 (PIG3) promoter (TGYCC)(15) motif.
abstract: The promoter of p53 induced gene 3 (PIG3) contains a variable number of tandem repeats (VNTRs) of pentanucleotides (TGYCC)n that is known as a p53 binding site. In this study, we investigated whether other potential molecules could bind to this PIG3 promoter (TGYCC)n motif. Ligand-chromatography combined with liquid chromatography-tandem mass spectrometry analyses indicated direct interactions of prohibitin and/or prohibiton with the (TGYCC)15 motif, which was confirmed by electrophoretic mobility shift assay and super-gel shift analysis with anti-prohibitin and anti-prohibiton antibodies. Using the chromatin immunopercipipation assay, we further demonstrated that prohibitin and prohibiton associated with the (TGYCC)15 motif in vivo regardless of the p53 status and apoptotic stress. We also found that prohibitin and prohibiton up-regulated PIG3 transcription independent of p53, although p53 obviously enhanced this process, and that the knock-down of prohibitin and prohibiton inhibited camptothecin-induced apoptosis. Taken together, our findings suggest that prohibitin and prohibiton contribute to PIG3-mediated apoptosis by binding to the PIG3 promoter (TGYCC)15 motif.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China. Electronic address: xguan@nju.edu.cn.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
authors.affiliation: Duke Cancer Institute, Duke University School of Medicine, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, Comprehensive Cancer Center, University of Michigan Medical School, USA.
authors.forename: Luo
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Johnson
authors.affiliation: Duke Cancer Institute, Duke University School of Medicine, USA. Electronic address: qingyi.wei@duke.edu.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D000091402:Prohibitins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000091402:Prohibitins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C495901:TP53 protein, human; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53
keywords: (TGYCC)n motif; PIG3; Prohibitin; Prohibiton