Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20 Slp1  under stress.
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 Slp1 Cdc20 , the co-activator of APC/C. Phosphorylation of Slp1 Cdc20  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.
Sun L, Chen X, Song C, Shi W, Liu L, Bai S, Wang X, Chen J, Jiang C, Wang SM, Luo ZQ, Wang R, Wang Y, Jin QW