Mechanism of degradation of CPEB during Xenopus oocyte maturation

Daiki Setoyama, Masakane Yamashita, Noriyuki Sagata

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

CPEB, a cytoplasmic polyadenylation element-binding protein, plays an important role in translational control of maternal mRNAs in early animal development. During Xenopus oocyte maturation, CPEB undergoes a Cdc2-mediated phosphorylation- and ubiquitin-dependent degradation that is required for proper entry into meiosis II. However, the precise mechanism of CPEB degradation, including the identity of the responsible E3 ubiquitin ligase, is not known. Here, we show that the SCFβ-TrCP E3 ubiquitin ligase complex targets CPEB for degradation during Xenopus oocyte maturation. β-TrCP, the F-box protein of SCFβ-TrCP, specifically binds to a sequence 190TSGFSS195 (termed here the TSG motif) of CPEB, thereby targeting CPEB for degradation. β-TrCP binding depends on phosphorylation of Thr-190, Ser-191, and Ser-195 in the TSG motif. Among these residues, Ser-191 is phosphorylated by the Polo-like kinase Plx1, which binds CPEB at a specific Thr-125 residue prephosphorylated by Cdc2. Finally, Cdc2-mediated phosphorylation of other multiple Ser residues, previously implicated in CPEB degradation, is required for both Thr-125 phosphorylation and β-TrCP binding, presumably causing conformational changes of CPEB. We propose that Cdc2 and Plx1 sequentially phosphorylate CPEB and target it for SCF β-TrCP-dependent degradation in Xenopus oocytes. We suggest that many other proteins carrying the TSG-like motif may be targeted by SCF β-TrCP.

Original languageEnglish
Pages (from-to)18001-18006
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number46
DOIs
Publication statusPublished - Nov 13 2007

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Xenopus
Oocytes
Phosphorylation
Ubiquitin-Protein Ligases
Stored Messenger RNA
F-Box Proteins
Polyadenylation
Meiosis
Ubiquitin
Carrier Proteins
Phosphotransferases
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Mechanism of degradation of CPEB during Xenopus oocyte maturation. / Setoyama, Daiki; Yamashita, Masakane; Sagata, Noriyuki.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 46, 13.11.2007, p. 18001-18006.

Research output: Contribution to journalArticle

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