DOI: 10.1101/gad.9.6.639. Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution.

Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution.

10.1101/gad.9.6.639

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Progression through the cell cycle is catalyzed by cyclin-dependent kinases (CDKs) and is negatively controlled by CDK inhibitors (CDIs). We have isolated a new member of the p21CIP1/p27KIP1 CDI family and named it p57KIP2 to denote its apparent molecular mass and higher similarity to p27KIP1. Three distinct p57 cDNAs were cloned that differ at the start of their open reading frames and correspond to messages generated by the use of distinct splice acceptor sites. p57 is distinguished from p21 and p27 by its unique domain structure. Four distinct domains follow the heterogeneous amino-terminal region and include, in order, a p21/p27-related CDK inhibitory domain, a proline-rich (28% proline) domain, an acidic (36% glutamic or aspartic acid) domain, and a carboxy-terminal nuclear targeting domain that contains a putative CDK phosphorylation site and has sequence similarity to p27 but not to p21. Most of the acidic domain consists of a novel, tandemly repeated 4-amino acid motif. p57 is a potent inhibitor of G1- and S-phase CDKs (cyclin E-cdk2, cyclin D2-cdk4, and cyclin A-cdk2) and, to lesser extent, of the mitotic cyclin B-Cdc2. In mammalian cells, p57 localizes to the nucleus, associates with G1 CDK components, and its overexpression causes a complete cell cycle arrest in G1 phase. In contrast to the widespread expression of p21 and p27 in human tissues, p57 is expressed in a tissue-specific manner, as a 1.5-kb species in placenta and at lower levels in various other tissues and a 7-kb mRNA species observed in skeletal muscle and heart. The expression pattern and unique domain structure of p57 suggest that this CDI may play a specialized role in cell cycle control.

Bibliography

Lee, M. H., ReynisdÃ³ttir, I., & MassaguÃ©, J. (1995). Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes & Development, 9(6), 639â649.

Authors 3

M H Lee (first)
I Reynisdóttir (additional)
J Massagué (additional)

References 49 Referenced 658

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Dates

Type	When
Created	18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 9:31 p.m.)
Indexed	1 month, 1 week ago (July 11, 2025, 6:55 a.m.)
Issued	30 years, 5 months ago (March 15, 1995)
Published	30 years, 5 months ago (March 15, 1995)
Published Online	30 years, 5 months ago (March 15, 1995)
Published Print	30 years, 5 months ago (March 15, 1995)

Funders 0

None

BibTeX

@article{Lee_1995, title={Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution.}, volume={9}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.9.6.639}, DOI={10.1101/gad.9.6.639}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Lee, M H and Reynisdóttir, I and Massagué, J}, year={1995}, month=mar, pages={639–649} }

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