title: KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes.
abstract: An unresolved issue in genotoxic stress response is identification of induced regulatory proteins and how these activate tumor suppressor p53 to determine appropriate cell responses. Transcription factor KAISO was previously described to repress transcription following binding to methylated DNA. In this study, we show that KAISO is induced by DNA damage in p53-expressing cells and then interacts with the p53-p300 complex to increase acetylation of p53 K320 and K382 residues, although decreasing K381 acetylation. Moreover, the p53 with this particular acetylation pattern shows increased DNA binding and potently induces cell cycle arrest and apoptosis by activating transcription of CDKN1A (cyclin-dependent kinase inhibitor 1) and various apoptotic genes. Analogously, in Kaiso KO mouse embryonic fibroblast cells, p53-to-promoter binding and up-regulation of p21 and apoptosis gene expression is significantly compromised. KAISO may therefore be a critical regulator of p53-mediated cell cycle arrest and apoptosis in response to various genotoxic stresses in mammalian cells.
authors.affiliation: Brain Korea 21 Plus Project for Medical Sciences, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, SeoDaeMoon-Ku, Seoul 120-752, Korea;
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Koh
authors.affiliation: Department of Biomedical Sciences and Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Korea;
authors.forename: Dohyun
authors.initials: D
authors.lastname: Han
authors.affiliation: VA Boston Healthcare System and Department of Neurology, Boston University School of Medicine, Boston, MA 02130;
authors.forename: Hoon
authors.initials: H
authors.lastname: Ryu
authors.affiliation: Brain Korea 21 Plus Project for Medical Sciences, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, SeoDaeMoon-Ku, Seoul 120-752, Korea;
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Choi
authors.affiliation: Brain Korea 21 Plus Project for Medical Sciences, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, SeoDaeMoon-Ku, Seoul 120-752, Korea;
authors.forename: Bu-Nam
authors.initials: BN
authors.lastname: Jeon
authors.affiliation: Brain Korea 21 Plus Project for Medical Sciences, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, SeoDaeMoon-Ku, Seoul 120-752, Korea;
authors.forename: Min-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences and Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Korea;
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Mass Spectrometry Research Center, Korea Basic Science Institute, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Korea;
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3XQ, United Kingdom; and.
authors.forename: Lee
authors.initials: L
authors.lastname: Parry
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3XQ, United Kingdom; and.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Clarke
authors.affiliation: Department of Cell Biology, Vanderbilt University, Nashville, TN 37232-2175.
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
authors.affiliation: Brain Korea 21 Plus Project for Medical Sciences, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, SeoDaeMoon-Ku, Seoul 120-752, Korea; mwhur2@yuhs.ac.
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D019175:DNA Methylation; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C492254:ZBTB33 protein, human; D004247:DNA; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: KAISO; apoptosis; cell cycle arrest; p300; p53