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
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
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 - Sequence conservation
KW - p107
KW - pRB
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U2 - 10.1101/gad.9.14.1740
DO - 10.1101/gad.9.14.1740
M3 - Article
C2 - 7622038
AN - SCOPUS:0028983384
SN - 0890-9369
VL - 9
SP - 1740
EP - 1752
JO - Genes and Development
JF - Genes and Development
IS - 14
ER -