An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein

Hirschi, Alexander; Cecchini, Matthew; Steinhardt, Rachel C; Schamber, Michael R; Dick, Frederick A; Rubin, Seth M (2010). An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nature structural & molecular biology, 17(9), pp. 1051-7. New York, N.Y.: Nature Publishing Group 10.1038/nsmb.1868

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The phosphorylation state and corresponding activity of the retinoblastoma tumor suppressor protein (Rb) are modulated by a balance of kinase and phosphatase activities. Here we characterize the association of Rb with the catalytic subunit of protein phosphatase 1 (PP1c). A crystal structure identifies an enzyme docking site in the Rb C-terminal domain that is required for efficient PP1c activity toward Rb. The phosphatase docking site overlaps with the known docking site for cyclin-dependent kinase (Cdk), and PP1 competition with Cdk-cyclins for Rb binding is sufficient to retain Rb activity and block cell-cycle advancement. These results provide the first detailed molecular insights into Rb activation and establish a novel mechanism for Rb regulation in which kinase and phosphatase compete for substrate docking.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Cecchini, Marco Giovanni

ISSN:

1545-9993

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:10

Last Modified:

05 Dec 2022 14:00

Publisher DOI:

10.1038/nsmb.1868

PubMed ID:

20694007

Web of Science ID:

000281571000004

URI:

https://boris.unibe.ch/id/eprint/1247 (FactScience: 202401)

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