Faculty, Staff and Student Publications

Publication Date

1-28-2025

Journal

Cancer Reports

DOI

10.1016/j.celrep.2024.115157

PMID

39792558

PMCID

PMC11874628

PubMedCentral® Posted Date

3-3-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

ERK activity oscillates between sustained activation during oocyte formation and transient inactivation during oocyte maturation, fertilization, and early embryogenesis. Consequences of ectopic ERK activity upon oocyte maturation and in early embryogenesis are unknown. We show, in Caenorhabditis elegans, that ectopic ERK activity upon oocyte maturation (metaphase I oocytes) results in embryos with abnormalities in nuclear divisions leading to embryonic death. We uncover that ERK directly phosphorylates Polo-like kinase I (PLK-1), on Serine 404, to inhibit nuclear envelope breakdown (NEBD) in early embryogenesis. The RAS/ERK/PLK-1 pathway poisons zygotic NEBD and inhibits the merging of parental genomes, underlining the importance of turning off ERK prior to embryogenesis. Given the conserved nature of both ERK signaling to oocyte development and PLK1 to embryonic divisions, this work has implications for women undergoing in vitro fertilization (IVF) where ectopic ERK activation during superovulation through hormonal stimulation may diminish oocyte quality and influence zygotic development.

Keywords

Animals, Caenorhabditis elegans, Oocytes, Caenorhabditis elegans Proteins, Protein Serine-Threonine Kinases, Cell Nucleus Division, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Polo-Like Kinase 1, Embryonic Development, Female, Enzyme Activation, MAP Kinase Signaling System

Published Open-Access

yes

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