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TIS21/BTG2/PC3 is expressed through PKC-delta pathway and inhibits binding of cyclin B1-Cdc2 and its activity, independent of p53 expression.

Ryu, MS; Lee, MS; Hong, JW; Hahn, TR; Moon, E; Lim, IK
Experimental cell research, 299(1):159-170, 2004
Journal Title
Experimental cell research
Signal transduction pathway and a new function of TIS21/BTG2/PC3 were investigated in p53 null U937 cells; Expression of TIS21 by 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulation was mediated by PKC-delta activation, however, was strongly inhibited by cPKC isozymes. When U937 cells were treated with TPA+Go6976, but not TPA+Go6850, the level of TIS21 mRNA was maintained over that of TPA alone. When analyzed by FACS, TPA-induced G2/M arrest was significantly inhibited by Go6850, but not by Go6976, suggesting the involvement of TIS21 and nPKC isozymes. Indeed, PKC-delta was found to be a regulator of the G2/M arrest and TIS21 expression, confirmed by employing rottlerin and dnPKC-delta experiments. In vivo accumulation of TIS21 protein significantly induced cell death through caspase 3 activation, which was supported further by degradations of procaspase 3, full-length PKC-delta, pRB, and p21(WAF1) in TIS21DeltaC expresser. When the cells were synchronized by nocodazole, TIS21 overexpressers inhibited degradations of cyclin A and cyclin B1 in 3 h after release from the synchronization. Furthermore, TIS21 inhibited cyclin B1-Cdc2 binding and its kinase activity in vivo. In summary, TPA-induced TIS21 mRNA expression is mediated by PKC-delta, and TIS21 induces G2/M arrest and cell death by inhibiting cyclin B1-Cdc2 binding and the kinase activity through its binding to Cdc2.
MeSH terms
AnimalsCDC2 Protein Kinase/*metabolismCarbazoles/pharmacologyCaspase 3Caspases/metabolismCell Cycle/drug effects/physiologyCell Death/drug effects/geneticsCyclin A/metabolismCyclin B/*metabolismCyclin B1Cyclin-Dependent Kinase Inhibitor p21Cyclins/metabolismG2 Phase/drug effects/geneticsGenes, Tumor SuppressorHumansImmediate-Early Proteins/genetics/*metabolismIndoles/pharmacologyMaleimides/pharmacologyMiceNIH 3T3 CellsNocodazole/pharmacologyProtein Binding/drug effects/physiologyProtein Kinase C/*metabolismProtein Kinase C-deltaPyridines/pharmacologyRNA, Messenger/drug effects/metabolismRetinoblastoma Protein/metabolismSignal Transduction/drug effects/*physiologyTumor Suppressor Protein p53/*metabolismTumor Suppressor ProteinsU937 Cells
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Journal Papers > Research Organization > BK21
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
유, 민숙임, 인경
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