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
Full text not available from this repository. (Request a copy)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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