Xiong, Y., Hannon, G. J., Zhang, H., Casso, D., Kobayashi, R., Beach, D. (1993) p21 is a universal inhibitor of cyclin kinases. Nature, 366 (6456). pp. 701-704. ISSN 00280836 (ISSN)
Abstract
DEREGULATION of cell proliferation is a hallmark of neoplastic transformation. Alteration in growth control pathways must translate into changes in the cell-cycle regulatory machinery, but the mechanism by which this occurs is largely unknown. Compared with normal human fibroblasts, cells transformed with a variety of viral oncoproteins show striking changes in the subunit composition of the cyclin-dependent kinases (CDKs). In normal cells, CDKs exist predominantly in multiple quaternary complexes, each containing a CDK, cyclin, proliferating cell nuclear antigen and the p21 protein. However, in many transformed cells, proliferating cell nuclear antigen and p21 are lost from these multiprotein enzymes. Here we have investigated the significance of this phenomenon by molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle kinase complexes. We find that p21 inhibits the activity of each member of the cyclin/CDK family. Furthermore, overexpression of p21 inhibits the proliferation of mammalian cells. Our results indicate that p21 may be a universal inhibitor of cyclin kinases.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | cycline inhibitor protein protein kinase protein p21 article cell line cell transformation growth regulation insect nonhuman priority journal Amino Acid Sequence Animal Base Sequence Cell Cycle Cell Division Cloning, Molecular Cyclins DNA Mice Molecular Sequence Data Moths Protein Kinases Protein p53 Recombinant Proteins RNA, Messenger Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Insecta Mammalia |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types |
| CSHL Authors: | |
| Communities: | CSHL labs > Hannon lab |
| Depositing User: | Matt Covey |
| Date: | 1993 |
| Date Deposited: | 09 Jan 2013 17:37 |
| Last Modified: | 09 Jan 2013 17:37 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/26494 |
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