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1: Nat Cell Biol. 2007 Feb;9(2):225-32. Epub 2006 Dec 24.
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Erratum in:
  • Nat Cell Biol. 2007 Mar;9(3):353.

Comment in:
Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit.

Binné UK, Classon MK, Dick FA, Wei W, Rape M, Kaelin WG Jr, Näär AM, Dyson NJ.

Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts, MA 02129, USA.

The retinoblastoma protein (pRB) negatively regulates the progression from G1 to S phase of the cell cycle, in part, by repressing E2F-dependent transcription. pRB also possesses E2F-independent functions that contribute to cell-cycle control--for example, during pRB-mediated cell-cycle arrest pRB associates with Skp2, the F-box protein of the Skp1-Cullin-F-box protein (SCF) E3 ubiquitin ligase complex, and promotes the stability of the cyclin-dependent kinase-inhibitor p27(Kip1) through an unknown mechanism. Degradation of p27(Kip1) is mediated by ubiquitin-dependent targeting of p27(Kip1) by SCF -Skp2 (ref. 4). Here, we report a novel interaction between pRB and the anaphase-promoting complex/cyclosome (APC/C) that controls p27(Kip1) stability by targeting Skp2 for ubiquitin-mediated degradation. Cdh1, an activator of APC/C, not only interacts with pRB but is also required for a pRB-induced cell-cycle arrest. The results reveal an unexpected physical convergence between the pRB tumour-suppressor protein and E3 ligase complexes, and raise the possibility that pRB may direct APC/C to additional targets during pRB-mediated cell-cycle exit.

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PMID: 17187060 [PubMed - indexed for MEDLINE]