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

Alexander Hirschi, Matthew Cecchini, Rachel C. Steinhardt, Michael R. Schamber, Frederick A. Dick, Seth M. Rubin

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1051-1057
Number of pages7
JournalNature Structural and Molecular Biology
Volume17
Issue number9
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein'. Together they form a unique fingerprint.

  • Cite this