| RRC ID |
82747
|
| Author |
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.
|
| Title |
Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress.
|
| Journal |
Elife
|
| Abstract |
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.
|
| Volume |
13
|
| Published |
2024-10-16
|
| DOI |
10.7554/eLife.97896
|
| PII |
97896
|
| PMID |
39412391
|
| PMC |
PMC11483130
|
| MeSH |
Anaphase-Promoting Complex-Cyclosome* / metabolism
Cdc20 Proteins* / genetics
Cdc20 Proteins* / metabolism
Mitogen-Activated Protein Kinases* / genetics
Mitogen-Activated Protein Kinases* / metabolism
Phosphorylation
Schizosaccharomyces* / metabolism
Schizosaccharomyces pombe Proteins / genetics
Schizosaccharomyces pombe Proteins / metabolism
Stress, Physiological
|
| IF |
7.08
|
| Resource |
| Yeast |
FY7833 |
