TY - JOUR
T1 - Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome-mediated processing and degradation
AU - Gutierrez, Gustavo J.
AU - Vögtlin, Andrea
AU - Castro, Ana
AU - Ferby, Ingvar
AU - Salvagiotto, Giorgia
AU - Ronai, Ze'ev
AU - Lorca, Thierry
AU - Nebreda, Angel R.
N1 - Funding Information:
We thank J. Moore and T. Hunt (Cancer Research UK Clare Hall Laboratories, South Mimms, UK) for providing advice and reagents to perform DNA replication assays in cyclin-E-depleted extracts; E. Pogge von Strandmann (University of Cologne, Germany) for sending us the Xenopus Siah-2 cDNA; and O. Coux (CNRS-CRBM, France) for providing E1 enzymes, helpful suggestions and for critically reading the manuscript. A.R.N. acknowledges the grant BFU2004-03566 from the Ministerio de Educacion y Ciencia of Spain.
PY - 2006/10
Y1 - 2006/10
N2 - 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 SCFβTrCP 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-3β, 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.
AB - 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 SCFβTrCP 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-3β, 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.
UR - http://www.scopus.com/inward/record.url?scp=33749177880&partnerID=8YFLogxK
U2 - 10.1038/ncb1472
DO - 10.1038/ncb1472
M3 - Article
C2 - 16964245
AN - SCOPUS:33749177880
SN - 1465-7392
VL - 8
SP - 1084
EP - 1094
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 10
ER -