A COMPLEX BETWEEN E2F AND THE PRB-RELATED PROTEIN P130 IS SPECIFICALLY TARGETED BY THE SIMIAN-VIRUS-40 LARGE T-ANTIGEN DURING CELL-TRANSFORMATION

被引:0
作者
WOLF, DA
HERMEKING, H
ALBERT, T
HERZINGER, T
KIND, P
EICK, D
机构
[1] GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT,INST KLIN MOLEK BIOL & TUMORGENET,D-81377 MUNICH,GERMANY
[2] UNIV MUNICH,DERMATOL KLIN & POLIKLIN,MOLEK PATHOL ABT,D-80337 MUNICH,GERMANY
关键词
TRANSFORMATION; E2F; P130; SV40 LARGE T ANTIGEN; CELL CYCLE;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is a negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.
引用
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页码:2067 / 2078
页数:12
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