Physical interaction of the retinoblastoma protein with human D cyclins

  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},

Figures and Tables from this paper

Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes.

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.

Functions of the retinoblastoma protein.

  • W. Kaelin
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1999
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.

The D-type cyclins and their role in tumorigenesis

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.

Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein.

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.

Functional Inactivation of the Retinoblastoma Protein Requires Sequential Modification by at Least Two Distinct Cyclin-cdk Complexes

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.

Gi Cyclins Control the Retinoblastoma Gene Product Growth Regulation Activity via Upstream Mechanisms 1

Using in vivo expression systems, it is shown that cyclins A, E, , D2, and D3 each function to phosphorylate and inactivate pRb, and coexpression of Gi cyclins and kinases represses pRB-mediated growth inhibition in Saos-2 cells.

Dual Cyclin-Binding Domains Are Required for p107 To Function as a Kinase Inhibitor

In vivo and in vitro evidence is presented to suggest that p107 is a bona fide inhibitor of both cyclin A-CDk2 and cyclin E-cdk2 that exhibits an inhibitory constant comparable to that of the cdk inhibitor p21/WAF1.



Regulation of retinoblastoma protein functions by ectopic expression of human cyclins

The retinoblastoma protein physically associates with the human cdc2 kinase

Results suggest that this kinase identified as the cell cycle-regulating kinase p34cdc2 or a closely related enzyme is one of the major regulators of pRB.

Association of human cyclin E with a periodic G1-S phase protein kinase.

The cyclin E-Cdk2 complex may constitute a human G1-S phase-specific regulatory protein kinase, which controls the G1 to S phase transition in budding yeast.

Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor

It is demonstrated that the Rb protein forms a complex with a DNA-bound transcription factor, and suggests that theRb protein might act by regulating transcription, which is thought to inactivate the growth-suppressing properties of the R b protein.

The retinoblastoma protein is phosphorylated on multiple sites by human cdc2.

Using tryptic phosphopeptide mapping, it is shown that pRB is phosphorylated on multiple serine and threonine residues in vivo and that many of these phosphorylation events can be mimicked in vitro using purified p34cdc2.