Meiotic regulation of the CDK activator RINGO/Speedy by ubiquitin-proteasome-mediated processing and degradation.
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(betaTrCP) 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-3beta, 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.
Gutierrez
Gustavo J
GJ
EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. gustavo@burnham.org
Vögtlin
Andrea
A
Castro
Ana
A
Ferby
Ingvar
I
Salvagiotto
Giorgia
G
Ronai
Ze'ev
Z
Lorca
Thierry
T
Nebreda
Angel R
AR
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D005260:Female; D016195:G2 Phase; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008540:Meiosis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
D018797:Cell Cycle Proteins; D025801:Ubiquitin; D029867:Xenopus Proteins; C119055:ls27 protein, Xenopus; D044843:SKP Cullin F-Box Protein Ligases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D017868:Cyclic AMP-Dependent Protein Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex