Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit.
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.
Mesh Terms:
Anaphase, Cadherins, Cell Cycle, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p27, G1 Phase, Humans, Retinoblastoma Protein, S Phase, S-Phase Kinase-Associated Proteins, Ubiquitin, Ubiquitin-Protein Ligase Complexes
Anaphase, Cadherins, Cell Cycle, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p27, G1 Phase, Humans, Retinoblastoma Protein, S Phase, S-Phase Kinase-Associated Proteins, Ubiquitin, Ubiquitin-Protein Ligase Complexes
Nat. Cell Biol.
Date: Feb. 01, 2007
PubMed ID: 17187060
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