Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein

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2006
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Sabile, Abdelmajid
Wirbelauer, Christiane
Hess, Daniel
Kogel, Ulrike
Krek, Wilhelm
Meyer, Andrea M.
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Molecular and Cellular Biology. 2006, 26(16), pp. 5994-6004. ISSN 0270-7306. Available under: doi: 10.1128/MCB.01630-05
Zusammenfassung

Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 provides a powerful route for enforcing normal progression through the mammalian cell cycle. According to a current model, the ubiquitination of p27 during S-phase progression is mediated by SCFSkp2 E3 ligase that captures Thr187-phosphorylated p27 by means of the F-box protein Skp2, which in turn couples the bound substrate via Skp1 to a catalytic core complex composed of Cul1 and the Rbx/Roc RING finger protein. Here we identify Skp2 as a component of an Skp1-cullin-F-box complex that is based on a Cul1-Ro52 RING finger B-box coiled-coil motif family protein catalytic core. Ro52-containing complexes display E3 ligase activity and promote the ubiquitination of Thr187-phosphorylated p27 in a RING-dependent manner in vitro. The knockdown of Ro52 expression in human cells with small interfering RNAs causes the accumulation of p27 and the failure of cells to enter S phase. Importantly, these effects are abrogated by the simultaneous removal of p27. Taken together, these data suggest a key role for Ro52 RING finger protein in the regulation of p27 degradation and S-phase progression in mammalian cells and provide evidence for the existence of a Cul1-based catalytic core that utilizes Ro52 RING protein to promote ubiquitination.

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570 Biowissenschaften, Biologie
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ISO 690SABILE, Abdelmajid, Christiane WIRBELAUER, Daniel HESS, Ulrike KOGEL, Martin SCHEFFNER, Wilhelm KREK, Andrea M. MEYER, 2006. Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein. In: Molecular and Cellular Biology. 2006, 26(16), pp. 5994-6004. ISSN 0270-7306. Available under: doi: 10.1128/MCB.01630-05
BibTex
@article{Sabile2006-08Regul-16767,
  year={2006},
  doi={10.1128/MCB.01630-05},
  title={Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein},
  number={16},
  volume={26},
  issn={0270-7306},
  journal={Molecular and Cellular Biology},
  pages={5994--6004},
  author={Sabile, Abdelmajid and Wirbelauer, Christiane and Hess, Daniel and Kogel, Ulrike and Scheffner, Martin and Krek, Wilhelm and Meyer, Andrea M.}
}
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