Journal
SCIENCE ADVANCES
Volume 8, Issue 7, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abl8861
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Funding
- Austrian Research Fund (FWF) [P 31275-B28]
- NIH [R35GM124895, R01 GM-100756]
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In this study, the phosphatase PPM-1.D/Wip1 is identified as a crucial substrate for PROM-1, and it regulates the initiation of meiotic prophase I by antagonizing CHK-2 kinase. PPM-1.D controls the amount of active CHK-2 through both catalytic and noncatalytic activities.
Transition from the stem/progenitor cell fate to meiosis is mediated by several redundant posttranscriptional regulatory pathways in Caenorhabditis elegans. Interfering with all three branches causes tumorous germ lines. SCFPROM-1 comprises one branch and mediates a scheduled degradation step at entry into meiosis. prom-1 mutants show defects in the timely initiation of meiotic prophase I events, resulting in high rates of embryonic lethality. Here, we identify the phosphatase PPM-1.D/Wip1 as crucial substrate for PROM-1. We report that PPM-1.D antagonizes CHK-2 kinase, a key regulator for meiotic prophase initiation, including DNA double-strand breaks, chromosome pairing, and synaptonemal complex formation. We propose that PPM-1.D controls the amount of active CHK-2 via both catalytic and noncatalytic activities; notably, noncatalytic regulation seems to be crucial at meiotic entry. PPM-1.D sequesters CHK-2 at the nuclear periphery, and programmed SCFPROM-1-mediated degradation of PPM-1.D liberates the kinase and promotes meiotic entry.
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