p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F

Liang Zhu, Ed Harlow, Brian David Dynlacht

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

The kinase activities of the cyclin/cdk complexes can be regulated in a number of ways. The most recently discovered mechanism of regulation is the association of cdk inhibitors (CKIs), such as p21, p27, and p57, with these complexes. In this report we demonstrate that the pRB-related protein p107, like the p21 family of cdk inhibitors, can inhibit the phosphorylation of target substrates by cyclin A/cdk2 and cyclin E/cdk2 complexes, and the associations of p 107 and p21 with cyclin/cdk2 rely on a structurally and functionally related interaction domain. Furthermore, interactions between p107 or p21 with cyclin/cdk2 complexes are mutually exclusive. In cells treated with DNA-damaging agents elevated levels of p21 cause a dissociation of p 107/cyclin/cdk2 complexes to yield p21/cyclin/cdk2 complexes. Finally, the consequences of cyclin/cdk2 interactions with p107 have been examined. The activation of the p107-bound cyclin/cdk kinases leads to dissociation of p107 from the transcription factor E2F. Together, these results suggest that cyclin/cdk complexes can be regulated by protein molecules from different families in a mutually exclusive manner in response to certain signals and that these inhibitory proteins may have a potential role in regulating macromolecular assembly.

Original languageEnglish (US)
Pages (from-to)1740-1752
Number of pages13
JournalGenes and Development
Volume9
Issue number14
StatePublished - Jul 15 1995
Externally publishedYes

Fingerprint

Cyclins
Phosphotransferases
E2F Transcription Factors
Cyclin A
Cyclin E
Proteins
Phosphorylation
DNA

Keywords

  • Cyclin-dependent kinase inhibitor (CKI)
  • Cyclin-dependent-kinase (cdk)
  • p107
  • pRB
  • Sequence conservation

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. / Zhu, Liang; Harlow, Ed; Dynlacht, Brian David.

In: Genes and Development, Vol. 9, No. 14, 15.07.1995, p. 1740-1752.

Research output: Contribution to journalArticle

Zhu, Liang ; Harlow, Ed ; Dynlacht, Brian David. / p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. In: Genes and Development. 1995 ; Vol. 9, No. 14. pp. 1740-1752.
@article{15527d208bc64b1cad2e3f570507df23,
title = "p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F",
abstract = "The kinase activities of the cyclin/cdk complexes can be regulated in a number of ways. The most recently discovered mechanism of regulation is the association of cdk inhibitors (CKIs), such as p21, p27, and p57, with these complexes. In this report we demonstrate that the pRB-related protein p107, like the p21 family of cdk inhibitors, can inhibit the phosphorylation of target substrates by cyclin A/cdk2 and cyclin E/cdk2 complexes, and the associations of p 107 and p21 with cyclin/cdk2 rely on a structurally and functionally related interaction domain. Furthermore, interactions between p107 or p21 with cyclin/cdk2 complexes are mutually exclusive. In cells treated with DNA-damaging agents elevated levels of p21 cause a dissociation of p 107/cyclin/cdk2 complexes to yield p21/cyclin/cdk2 complexes. Finally, the consequences of cyclin/cdk2 interactions with p107 have been examined. The activation of the p107-bound cyclin/cdk kinases leads to dissociation of p107 from the transcription factor E2F. Together, these results suggest that cyclin/cdk complexes can be regulated by protein molecules from different families in a mutually exclusive manner in response to certain signals and that these inhibitory proteins may have a potential role in regulating macromolecular assembly.",
keywords = "Cyclin-dependent kinase inhibitor (CKI), Cyclin-dependent-kinase (cdk), p107, pRB, Sequence conservation",
author = "Liang Zhu and Ed Harlow and Dynlacht, {Brian David}",
year = "1995",
month = "7",
day = "15",
language = "English (US)",
volume = "9",
pages = "1740--1752",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "14",

}

TY - JOUR

T1 - p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F

AU - Zhu, Liang

AU - Harlow, Ed

AU - Dynlacht, Brian David

PY - 1995/7/15

Y1 - 1995/7/15

N2 - The kinase activities of the cyclin/cdk complexes can be regulated in a number of ways. The most recently discovered mechanism of regulation is the association of cdk inhibitors (CKIs), such as p21, p27, and p57, with these complexes. In this report we demonstrate that the pRB-related protein p107, like the p21 family of cdk inhibitors, can inhibit the phosphorylation of target substrates by cyclin A/cdk2 and cyclin E/cdk2 complexes, and the associations of p 107 and p21 with cyclin/cdk2 rely on a structurally and functionally related interaction domain. Furthermore, interactions between p107 or p21 with cyclin/cdk2 complexes are mutually exclusive. In cells treated with DNA-damaging agents elevated levels of p21 cause a dissociation of p 107/cyclin/cdk2 complexes to yield p21/cyclin/cdk2 complexes. Finally, the consequences of cyclin/cdk2 interactions with p107 have been examined. The activation of the p107-bound cyclin/cdk kinases leads to dissociation of p107 from the transcription factor E2F. Together, these results suggest that cyclin/cdk complexes can be regulated by protein molecules from different families in a mutually exclusive manner in response to certain signals and that these inhibitory proteins may have a potential role in regulating macromolecular assembly.

AB - The kinase activities of the cyclin/cdk complexes can be regulated in a number of ways. The most recently discovered mechanism of regulation is the association of cdk inhibitors (CKIs), such as p21, p27, and p57, with these complexes. In this report we demonstrate that the pRB-related protein p107, like the p21 family of cdk inhibitors, can inhibit the phosphorylation of target substrates by cyclin A/cdk2 and cyclin E/cdk2 complexes, and the associations of p 107 and p21 with cyclin/cdk2 rely on a structurally and functionally related interaction domain. Furthermore, interactions between p107 or p21 with cyclin/cdk2 complexes are mutually exclusive. In cells treated with DNA-damaging agents elevated levels of p21 cause a dissociation of p 107/cyclin/cdk2 complexes to yield p21/cyclin/cdk2 complexes. Finally, the consequences of cyclin/cdk2 interactions with p107 have been examined. The activation of the p107-bound cyclin/cdk kinases leads to dissociation of p107 from the transcription factor E2F. Together, these results suggest that cyclin/cdk complexes can be regulated by protein molecules from different families in a mutually exclusive manner in response to certain signals and that these inhibitory proteins may have a potential role in regulating macromolecular assembly.

KW - Cyclin-dependent kinase inhibitor (CKI)

KW - Cyclin-dependent-kinase (cdk)

KW - p107

KW - pRB

KW - Sequence conservation

UR - http://www.scopus.com/inward/record.url?scp=0028983384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028983384&partnerID=8YFLogxK

M3 - Article

C2 - 7622038

AN - SCOPUS:0028983384

VL - 9

SP - 1740

EP - 1752

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 14

ER -