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| Item Type: | Article |
|---|---|
| Title: | p21WAF1/CIP1 mutants deficient in inhibiting cyclin-dependent kinases (CDKs) can promote assembly of active cyclin D/CDK4(6) complexes in human tumor cells1 |
| Creators Name: | Welcker, M., Lukas, J., Strauss, M. and Bartek, J. |
| Abstract: | The cyclin-dependent kinase (CDK) inhibitor p21WAF1/CIP1 is a multidomain, multifunctional protein and a candidate tumor suppressor. Here, we show that, among rationally designed and tumor-associated mutants of human p21 ectopically expressed in U-2-OS cells, those that are selectively deficient in binding to either cyclin or CDK are partially impaired in inhibiting endogenous CDK activities but efficiently promote assembly of active cyclin D/CDK4(6) complexes. These results provide mechanistic insights into the p21-cyclin/CDK interplay in vivo and suggest a functional subclassification of tumor-specific aberrations of p21. Intriguingly, the subclass exemplified by the melanoma-derived N50S mutant may promote tumorigenesis, by both attenuating CDK-inhibitory function and concomitantly activating the proto-oncogenic cyclin D-dependent kinases. |
| Keywords: | Cyclins, Tumor Suppressor Genes, Melanoma, Neoplasm Proteins, Point Mutation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Cultured Tumor Cells |
| Source: | Cancer Research |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Volume: | 58 |
| Number: | 22 |
| Page Range: | 5053-5056 |
| Date: | 15 November 1998 |
| Official Publication: | http://cancerres.aacrjournals.org/content/58/22/5053.abstract |
| PubMed: | View item in PubMed |
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