Physical interaction of the retinoblastoma protein with human D cyclins

@article{Dowdy1993PhysicalIO,
  title={Physical interaction of the retinoblastoma protein with human D cyclins},
  author={Steven F Dowdy and Philip Hinds and Kenway Louie and Steven I. Reed and Andrew Arnold and Robert A. Weinberg},
  journal={Cell},
  year={1993},
  volume={73},
  pages={499-511}
}
The retinoblastoma protein (pRb) functions as a regulator of cell proliferation and in turn is regulated by cyclin-dependent kinases. Cyclins D1 and D3 can form complexes with pRb that resemble those formed by several viral oncoproteins and are disrupted by the adenovirus E1A oncoprotein and derived peptides. These cyclins contain a sequence motif similar to the pRb-binding conserved region II motif of the viral oncoproteins. Alteration of this motif in cyclin D1 prevents formation of cyclin D1… Expand
Functional interactions of the retinoblastoma protein with mammalian D-type cyclins
TLDR
All D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known tumor suppressor. Expand
Physical interaction between pRb and cdk9/cyclinT2 complex
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The data suggest that, in logarithmically growing cells, cdk9/cyclin T2 and pRb are located in a nuclear multiprotein complex probably involved in transduction of cellular signals to the basal transcription machinery and that one of these signals could be thecdk9 phosphorylation of pR b. Expand
Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes.
TLDR
It is shown that phosphorylation of the pRb-related p107 results in the loss of the ability to associate with E2F-4, a transcription factor with growth-promoting and oncogenic activity, and that the activity of p107 is regulated by phosphorylated through D-type cyclins. Expand
Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks.
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  • Chemistry, Medicine
  • Biochimica et biophysica acta
  • 2001
TLDR
This review focuses on recent data to suggest that different pRB functions are progressively and cooperatively inactivated by multiple cyclin/cdk complexes during G1- and S-phase and the implications of such a model for pRB-mediated tumor suppression are discussed. Expand
Functions of the retinoblastoma protein.
  • W. Kaelin
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1999
TLDR
Emerging data suggest that combinatorial control of pRB function may be achieved through the use of different phosphoacceptor sites, different cyclin/cdk docking sites, and different cycline-dependent kinases. Expand
The D-type cyclins and their role in tumorigenesis
  • G. Peters
  • Biology, Medicine
  • Journal of Cell Science
  • 1994
TLDR
The D-cyclins preferentially associate with two closely related members of the cyclin-dependent kinase family, Cdk4 and Cdk6 and the various complexes are each capable of phosphorylating the retinoblastoma gene product, at least in vitro, suggesting that the growth promoting effects of the D- cyclins may be manifest via their interactions with tumour suppressor genes. Expand
Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein.
TLDR
It is shown that one of these mutations defines a domain in cyclin E necessary for phosphorylation of the retinoblastoma protein (Rb), confirming the idea that cyclins contribute to substrate recognition by cyclin-CDK complexes, demonstrating the utility of targeting mutants in the identification of essentialcyclin- CDK substrates, and putting Cyclin E squarely into the family of proteins designed to regulate Rb. Expand
Functional Inactivation of the Retinoblastoma Protein Requires Sequential Modification by at Least Two Distinct Cyclin-cdk Complexes
TLDR
It is shown that endogenous D-type cyclins, acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Expand
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. To identify potential Cdk2 regulators, we haveExpand
Gi Cyclins Control the Retinoblastoma Gene Product Growth Regulation Activity via Upstream Mechanisms 1
Inactivation of the retinoblastoma gene produd (pRb) occurs concomitant with the appearance of its hyperphosphorylated form in mid to late G1 . Multiple cyclin/CDK complexes are implicated in theExpand
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Functional interactions of the retinoblastoma protein with mammalian D-type cyclins
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All D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known tumor suppressor. Expand
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