Cloning of p57(KIP2), a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution Journal Article
| Authors: | Lee, M. H.; Reynisdottir, I.; Massague, J. |
| Article Title: | Cloning of p57(KIP2), a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution |
| 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 p21(CIP1)/p27(KIP1) CDI family and named it p57(KIP2) to denote its apparent molecular mass and higher similarity to p27(KIP1). 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. |
| Keywords: | human tissue; unclassified drug; genetics; dose response; nonhuman; molecular genetics; protein conformation; protein domain; protein localization; animal cell; mouse; animal; metabolism; mammalia; mice; cell cycle; cell compartmentalization; cell cycle progression; cell cycle s phase; complex formation; gene expression; nuclear protein; dose-response relationship, drug; enzyme inhibitor; physiology; animalia; nuclear proteins; molecular cloning; cloning, molecular; biosynthesis; chemistry; amino acid sequence; molecular sequence data; sequence homology, amino acid; tissue distribution; messenger rna; nucleotide sequence; protein p27; recombinant proteins; recombinant protein; alternative splicing; alternative rna splicing; cell strain cos1; epithelium cell; base sequence; cell nucleus; cycline; protein structure; sequence homology; cyclin-dependent kinases; cyclin a; cyclin b; cyclin dependent kinase; cyclin dependent kinase inhibitor; cell cycle phase; retinoblastoma protein; glutamic acid; protein p21; aspartic acid; s phase; cyclin-dependent kinase; fungal protein; cyclin e; proline; mink; cyclin d2; fungal proteins; microtubule-associated proteins; microtubule associated protein; mitosis inhibition; protein p57; histone h1; cdkn1b; human; priority journal; article; cell compartmentation; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; mustela vison; protamine kinase; cell cycle inhibitor; domain structure; cyclin dependent kinases; cyclin kinase inhibitor protein 2; microtubule associated proteins |
| Journal Title: | Genes and Development |
| Volume: | 9 |
| Issue: | 6 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 1995-03-15 |
| Start Page: | 639 |
| End Page: | 649 |
| Language: | English |
| DOI: | 10.1101/gad.9.6.639 |
| PUBMED: | 7729683 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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