TIS21/BTG2/PC3 is expressed through PKC-δ pathway and inhibits binding of cyclin B1-Cdc2 and its activity, independent of p53 expression
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- 作者：Ryu ; Min Sook ; Lee ; Myung Soog ; Hong ; Jong Wook ; Hahn ; Tae-Ryong ; Moon ; Eunpyo ; Lim ; In Kyoung
- 关键词：TIS21/BTG2/PC3 ; G2/M arrest ; PKC-δ ; Cyclin B1 ; Cdc2 ; U937 cells ; TIS21 ; TPA-inducible sequence 21 ; TPA ; 12-O-tetradecanoylphorbol-13-acetate ; BTG ; B-cell translocation gene ; PKC ; protein kinase C ; cPKC ; conventional PKC ; nPKC ; novel PKC ; d
- 刊名：Experimental Cell Research
- 出版年：2004
- 出版时间：September 10, 2004
- 年：2004
- 卷：299
- 期：1
- 页码：159-170
- 全文大小：1.10 M
文摘
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-δ 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-δ was found to be a regulator of the G2/M arrest and TIS21 expression, confirmed by employing rottlerin and dnPKC-δ 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-δ, pRB, and p21WAF1 in TIS21ΔC 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-δ, and TIS21 induces G2/M arrest and cell death by inhibiting cyclin B1-Cdc2 binding and the kinase activity through its binding to Cdc2.