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| The EMBO Journal
(2000) 19, 5362–5375, doi:10.1093/emboj/19.20.5362 |
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| The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts |
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| Christiane Wirbelauer1, Hedwig Sutterlüty1, Marc Blondel2, Mathias Gstaiger1, Matthias Peter2, Francoise Reymond1 and Wilhelm Krek1 |
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1 Friedrich Miescher Institut, Maulbeerstrasse 66, CH-4058 Basel, Switzerland 2 Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH-1066 Epalinges/VD, Switzerland To whom correspondence should be addressed Wilhelm Krek, wilhelm.krek@fmi.ch Received 19 April 2000; Revised 10 August 2000; Accepted 18 August 2000. |
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| Abstract |
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| The ubiquitin protein ligase SCFSkp2 is composed of Skp1, Cul1, Roc1/Rbx1 and the F-box protein Skp2, the substrate-recognition subunit. Levels of Skp2 decrease as cells exit the cell cycle and increase as cells re-enter the cycle. Ectopic expression of Skp2 in quiescent fibroblasts causes mitogen-independent S-phase entry. Hence, mechanisms must exist for limiting Skp2 protein expression during the G0/G1 phases. Here we show that Skp2 is degraded by the proteasome in G0/G1 and is stabilized when cells re-enter the cell cycle. Rapid degradation of Skp2 in quiescent cells depends on Skp2 sequences that contribute to Cul1 binding and interference with endogenous Cul1 function in serum-deprived cells induces Skp2 expression. Furthermore, recombinant Cul1–Roc1/Rbx1–Skp1 complexes can catalyse Skp2 ubiquitylation in vitro. These results suggest that degradation of Skp2 in G0/G1 is mediated, at least in part, by an autocatalytic mechanism involving a Skp2-bound Cul1-based core ubiquitin ligase and imply a role for this mechanism in the suppression of SCFSkp2 ubiquitin protein ligase function during the G0/G1 phases of the cell cycle. |
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| Keywords: cell cycle, cullin, proteasome, Skp2, ubiquitin |
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