title: PKCdelta modulates p21WAF1/CIP1 ability to bind to Cdk2 during TNFalpha-induced apoptosis.
abstract: Cyclin-dependent kinase 2 (Cdk2) activity is thought to be involved in cell death-associated chromatin condensation and other manifestations of apoptotic death. Here we show that during TNFalpha-induced apoptosis, PKCdelta is activated in a caspase-3-dependent manner and phosphorylates p21(WAF1/CIP1), a specific cyclin-dependent kinase inhibitor, on (146)Ser. This residue is located near a cyclin-binding motif (Cy2) that plays an important role in the interaction between p21(WAF1/CIP1) and Cdk2, and its phosphorylation modulates the ability of p21(WAF1/CIP1) to associate with Cdk2. The phosphorylation of p21(WAF1/CIP1) is temporally related to the activation kinetics of Cdk2 activity during the apoptosis. We propose that during TNFalpha-induced apoptosis, PKCdelta-mediated phosphorylation of p21(WAF1/CIP1) at (146)Ser attenuates the Cdk2 binding of p21(WAF1/CIP1) and thereby upregulates Cdk2 activity.
authors.affiliation: College of Pharmacy, Division of Pharmaceutical Biosciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: You-Take
authors.initials: YT
authors.lastname: Oh
authors.forename: Kwang Hoon
authors.initials: KH
authors.lastname: Chun
authors.forename: Jeong In
authors.initials: JI
authors.lastname: Oh
authors.forename: Jeong Ae
authors.initials: JA
authors.lastname: Park
authors.forename: Yong Ung
authors.initials: YU
authors.lastname: Kim
authors.forename: Seung Ki
authors.initials: SK
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D014409:Tumor Necrosis Factor-alpha; D051745:Protein Kinase C-delta; D051357:Cyclin-Dependent Kinase 2