title: Transcriptional activation of APAF1 by KAISO (ZBTB33) and p53 is attenuated by RelA/p65.
abstract: KAISO, a member of the POK protein family, is induced by DNA-damaging agents to enhance apoptosis in a p53-dependent manner. Previously, we found that p53 interacts with KAISO, and acetylation of p53 lysine residues by p300 is modulated by KAISO. APAF1, the core molecule of the apoptosome, is transcriptionally activated by KAISO only in cells expressing p53, which binds to APAF1 promoter p53-response elements (p53REs). APAF1 transcriptional upregulation is further enhanced by KAISO augmentation of p53 binding to the APAF1 promoter distal p53RE#1 (bp, -765 to -739). Interestingly, a NF-κB response element, located close to the p53RE#1, mediates APAF1 transcriptional repression by affecting interaction between KAISO and p53. Ectopic RelA/p65 expression led to depletion of nuclear KAISO, with KAISO being mainly detected in the cytoplasm. RelA/p65 cytoplasmic sequestration of KAISO prevents its nuclear interaction with p53, decreasing APAF1 transcriptional activation by a p53-KAISO-p300 complex in cells exposed to genotoxic stresses. While KAISO enhances p53-dependent apoptosis by increasing APAF1 gene expression, RelA/p65 decreases apoptosis by blocking interaction between KAISO and p53. These findings have relevance to the phenomenon of cancer cells' diminished apoptotic capacity and the onset of chemotherapy resistance.
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Koh
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Haemin
authors.initials: H
authors.lastname: An
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Bu-Nam
authors.initials: BN
authors.lastname: Jeon
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Yonseidae-gil, Wonju 220-710, Republic of Korea.
authors.forename: Sujin Susanne
authors.initials: SS
authors.lastname: Hur
authors.affiliation: Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Department of Biochemistry and Molecular Biology, Yonsei University School of Medicine, 50-1, Yonsei-Ro, SeoDaeMun-Gu, Seoul 120-752, Republic of Korea. Electronic address: mwhur2@yuhs.ac.
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; C495901:TP53 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C492254:ZBTB33 protein, human
keywords: APAF1; Apoptosis; DNA damage response; KAISO; p53