XB-ART-19960
Nature
1995 Mar 23;3746520:386-8. doi: 10.1038/374386a0.
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Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA.
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The protein p21 (WAF1, CIP1 or sdi1), induced by the tumour-suppressor protein p53, interacts with and inhibits two different targets essential for cell-cycle progression. One of these is the cyclin-Cdk family of kinases and the other is the essential DNA replication factor, proliferating-cell nuclear antigen (PCNA). We report here that separate domains of p21 are responsible for interacting with and inhibiting the two targets. An amino-terminal domain inhibits cyclin-Cdk kinases and a carboxy-terminal domain inhibits PCNA. Using these separated domains, we have determined that p21 inhibits different biological systems through different targets. The PCNA-binding domain is sufficient for inhibition of DNA replication based on simian virus 40, whereas the Cdk2-binding domain is sufficient for inhibition of DNA replication based on Xenopus egg extract and for growth suppression in transformed human cells.
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Species referenced: Xenopus
Genes referenced: cdk2 cdkn1a nsg1 pcna tp53