title: AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity.
abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences & Biochemistry & Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Choi
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Kang
authors.forename: Soon-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Hyung Soon
authors.initials: HS
authors.lastname: Park
authors.forename: Gum-Yong
authors.initials: GY
authors.lastname: Kang
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Bang
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051028:bcl-2-Associated X Protein; D012694:Serine; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D055372:AMP-Activated Protein Kinases