p21 is a universal inhibitor of cyclin kinases

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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8259214
DOI: 10.1038/366701a0

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: http://repository.cshl.edu/id/eprint/26494

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