Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress

Autor: Li Sun, Xuejin Chen, Chunlin Song, Wenjing Shi, Libo Liu, Shuang Bai, Xi Wang, Jiali Chen, Chengyu Jiang, Shuang-min Wang, Zhou-qing Luo, Ruiwen Wang, Yamei Wang, Quan-wen Jin
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: eLife, Vol 13 (2024)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.97896
Popis: Mitotic anaphase onset is a key cellular process tightly regulated by multiple kinases. The involvement of mitogen-activated protein kinases (MAPKs) in this process has been established in Xenopus egg extracts. However, the detailed regulatory cascade remains elusive, and it is also unknown whether the MAPK-dependent mitotic regulation is evolutionarily conserved in the single-cell eukaryotic organisms such as fission yeast (Schizosaccharomyces pombe). Here, we show that two MAPKs in S. pombe indeed act in concert to restrain anaphase-promoting complex/cyclosome (APC/C) activity upon activation of the spindle assembly checkpoint (SAC). One MAPK, Pmk1, binds to and phosphorylates Slp1Cdc20, the co-activator of APC/C. Phosphorylation of Slp1Cdc20 by Pmk1, but not by Cdk1, promotes its subsequent ubiquitylation and degradation. Intriguingly, Pmk1-mediated phosphorylation event is also required to sustain SAC under environmental stress. Thus, our study establishes a new underlying molecular mechanism of negative regulation of APC/C by MAPK upon stress stimuli, and provides a previously unappreciated framework for regulation of anaphase entry in eukaryotic cells.
Databáze: Directory of Open Access Journals