Cell-cycle inhibition by independent CDK and PCNA binding domains in p21(cip1) Journal Article

  


Authors: Luo, Y.; Hurwitz, J.; Massagué, J.
Article Title: Cell-cycle inhibition by independent CDK and PCNA binding domains in p21(cip1)
Abstract: MAMMALIAN cell-cycle control by antimitogenic signals involves p21Cip1/WAF1(refs 1-4), p27Kip1 (refs 5, 6) andp57Kip2(refs 7, 8) a family of proteins that bind to and inhibit cyclin-dependent kinases (CDKs) required for initiation of S phase. The protein p21 also binds to the DNA polymerase δ processivity factor, proliferating-cell nuclear antigen (PCNA), and inhibits in vitro PCNA-dependent DNA replication9, 10. The CDK and PCNA inhibitory activities of p21 are shown here to be functionally independent and to reside in separate protein domains. The PCNA binding and inhibitory activities, which are not observed with p27 or p57, reside in the C-terminal domain of p21, whereas the CDK inhibitory activity resides in the conserved N-terminal domains of these proteins. When separately overexpressed in mammalian cells, the CDK and PCNA inhibitory domains prevent DNA replication, demonstrating a dual function of p21 as a cell-cycle inhibitor in vivo. © 1995 Nature Publishing Groups. All Rights Reserved.
Keywords: controlled study; nonhuman; protein domain; animal cell; animal; mice; cell cycle; cell cycle s phase; dna; amino acid sequence; molecular sequence data; amino terminal sequence; recombinant fusion proteins; protein-serine-threonine kinases; binding sites; cycline; protein family; cyclin-dependent kinases; cyclins; cyclin dependent kinase; protein p21; genetic conservation; mammal cell; proliferating cell nuclear antigen; dna directed dna polymerase delta; cell nucleus antigen; antimitotic agent; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Nature
Volume: 375
Issue: 6527
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 1995-05-11
Start Page: 159
End Page: 161
Language: English
DOI: 10.1038/375159a0
PUBMED: 7753174
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029063745&doi=10.1038%2f375159a0&partnerID=40&md5=d85b2288631752c084b526705a7fc379
Notes: Letter -- Export Date: 28 August 2018 -- Source: Scopus
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MSK Authors
  1. Jerard Hurwitz
    206 Hurwitz
  2. Joan Massague
    388 Massague
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