Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit

Nat Cell Biol. 2007 Feb;9(2):225-32. doi: 10.1038/ncb1532. Epub 2006 Dec 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase*
  • Anaphase-Promoting Complex-Cyclosome
  • Cadherins / metabolism
  • Cell Cycle
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • G1 Phase
  • Humans
  • Retinoblastoma Protein / metabolism*
  • S Phase
  • S-Phase Kinase-Associated Proteins / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism*


  • Cadherins
  • Retinoblastoma Protein
  • S-Phase Kinase-Associated Proteins
  • Ubiquitin
  • Cyclin-Dependent Kinase Inhibitor p27
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome