title: Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis.
abstract: LATS2 (Large tumor suppressor 2), a member of the conserved AGC Ser/Thr (S/T) kinase family, is a human tumor suppressor gene. Here, we show that in response to ultraviolet radiation, Lats2 is phosphorylated by Chk1 at Ser835 (S835), which is located in the kinase domain of Lats2. This phosphorylation enhances Lats2 kinase activity. Subsequently, Lats2 phosphorylates p21 at S146. p21 (CDKN1A) is a cyclin-dependent kinase (CDK) inhibitor, which not only regulates the cell cycle by inhibition of CDK, but also inhibits apoptosis by binding to procaspase-3 in the cytoplasm. Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis. Accordingly, Lats2 overexpression induces p21 degradation, activation of caspase-3 and caspase-9, and apoptosis. These findings describe a novel Lats2-dependent mechanism for induction of cell death in response to severe DNA damage.
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yabuta
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Okada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Torigata
authors.forename: Yael
authors.initials: Y
authors.lastname: Aylon
authors.forename: Moshe
authors.initials: M
authors.lastname: Oren
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
mesh_terms: D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D015536:Down-Regulation; D004789:Enzyme Activation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism* / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C406449:LATS2 protein, human; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; CDKN1A; Lats2; Phosphorylation; UV; p21