RRC ID 53959
著者 Kisielnicka E, Minasaki R, Eckmann CR.
タイトル MAPK signaling couples SCF-mediated degradation of translational regulators to oocyte meiotic progression.
ジャーナル Proc Natl Acad Sci U S A
Abstract RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway that subjects two nonrelated but broadly evolutionarily conserved translational regulators (CPB-3/CPEB and GLD-1/STAR) to proteosomal degradation in Caenorhabditis elegans germ cells at the transition from pachytene to diplotene of meiotic prophase. Both RBPs are recognized by the same ubiquitin ligase complex, containing the molecular scaffold Cullin-1 and the tumor suppressor SEL-10/FBXW7 as its substrate recognition subunit. Destabilization of either RBP through this Skp, Cullin, F-box-containing complex (SCF) ubiquitin ligase appears to loosen its negative control over established target mRNAs, and presumably depends on a prior phosphorylation of CPB-3 and GLD-1 by MAPK (MPK-1), whose activity increases in mid- to late pachytene to promote meiotic progression and oocyte differentiation. Thus, we propose that the orchestrated degradation of RBPs via MAPK-signaling cascades during germ cell development may act to synchronize meiotic with sexual differentiation gene expression changes.
巻・号 115(12)
ページ E2772-E2781
公開日 2018-3-20
DOI 10.1073/pnas.1715439115
PII 1715439115
PMID 29496961
PMC PMC5866554
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism MAP Kinase Signaling System Meiosis / physiology* Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism Oocytes / metabolism Oocytes / physiology* Oogenesis / physiology Phosphorylation Protein Processing, Post-Translational RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Ubiquitin-Protein Ligases / metabolism Ubiquitination
IF 9.412
引用数 5
リソース情報
線虫 tm1746