Nature Cell Biology
- 8, 1084 - 1094 (2006)
Published online: 10 September 2006; | doi:10.1038/ncb1472
Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome-mediated processing and degradationGustavo J. Gutierrez1, 2, Andrea Vögtlin1, 3, Ana Castro4, Ingvar Ferby1, 5, Giorgia Salvagiotto1, 6, Ze'ev Ronai2, Thierry Lorca4 & Angel R. Nebreda1, 71
EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. 2
BIMR, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. 3
Institute of Virology, Veterinary Medical Faculty, University of Zurich, Winterthurerstrasse 266a, CH-8057 Zurich, Switzerland. 4
CRBM-CNRS, 1919 Route de Mende, 34096 Montpellier, France. 5
Max-Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany. 6
IMP, Dr. Bohr-Gasse 7, 1030 Vienna, Austria. 7
CNIO (Spanish National Cancer Center), Melchor Fernandez Almagro, 3, E-28029 Madrid, Spain.
Correspondence should be addressed to anebreda@cnio.es or Gustavo J. GutierrezAngel R. Nebreda gustavo@burnham.org
Xenopus RINGO/Speedy (XRINGO) is a potent inducer of oocyte meiotic maturation that can directly activate Cdk1 and Cdk2. Here, we show that endogenous XRINGO protein accumulates transiently during meiosis I entry and then is downregulated. This tight regulation of XRINGO expression is the consequence of two interconnected mechanisms: processing and degradation. XRINGO processing involves recognition of at least three distinct phosphorylated recognition motifs by the SCF TrCP ubiquitin ligase, followed by proteasome-mediated limited degradation, resulting in an amino-terminal XRINGO fragment. XRINGO processing is directly stimulated by several kinases, including protein kinase A and glycogen synthase kinase-3 , and may contribute to the maintenance of G2 arrest. On the other hand, XRINGO degradation after meiosis I is mediated by the ubiquitin ligase Siah-2, which probably requires phosphorylation of XRINGO on Ser 243 and may be important for the omission of S phase at the meiosis-I–meiosis-II transition in Xenopus oocytes.
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