INTERACTION OF THE P53-REGULATED PROTEIN GADD45 WITH PROLIFERATING CELL NUCLEAR ANTIGEN

INTERACTION OF THE P53-REGULATED PROTEIN GADD45 WITH PROLIFERATING CELL NUCLEAR ANTIGEN
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DOI:
10.1126/science.7973727
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发表时间:
1994-11-25
期刊:
影响因子:
56.9
通讯作者:
FORNACE, AJ
FORNACE, AJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SMITH, ML;CHEN, IT;FORNACE, AJ

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GADD 45是一种广泛表达的哺乳动物基因,由DNA损伤和某些其他应激诱导。与另一个p53调节基因p21(WAF 1/CIP 1)一样,GADD 45与生长抑制相关,其产物与细胞周期蛋白依赖性激酶(Cdk)和增殖细胞核抗原(PCNA)结合。Gadd 45被发现与PCNA结合,PCNA是Cdk复合物的正常组分,也是参与DNA复制和修复的蛋白质。Gadd 45在体外刺激DNA切除修复,抑制细胞进入S期。这些结果确立了GADD 45作为p53依赖性细胞周期检查点和DNA修复之间的联系。
GADD45 is a ubiquitously expressed mammalian gene that is induced by DNA damage and certain other stresses. Like another p53-regulated gene, p21(WAF1/CIP1), whose product binds to cyclin-dependent kinases (Cdk's) and proliferating cell nuclear antigen (PCNA), GADD45 has been associated with growth suppression. Gadd45 was found to bind to PCNA, a normal component of Cdk complexes and a protein involved in DNA replication and repair. Gadd45 stimulated DNA excision repair in vitro and inhibited entry of cells into S phase. These results establish GADD45 as a link between the p53-dependent cell cycle checkpoint and DNA repair.