Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit
- 24 December 2006
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 9 (2), 225-232
- https://doi.org/10.1038/ncb1532
Abstract
The retinoblastoma protein (pRB) negatively regulates the progression from G1 to S phase of the cell cycle, in part, by repressing E2F-dependent transcription1. 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 p27Kip1 through an unknown mechanism2,3. Degradation of p27Kip1 is mediated by ubiquitin-dependent targeting of p27Kip1 by SCF –Skp2 (ref. 4). Here, we report a novel interaction between pRB and the anaphase-promoting complex/cyclosome (APC/C) that controls p27Kip1 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.Keywords
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