Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20^Slp1 under stress

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Mitotic anaphase onset is a critical cell cycle stage regulated by kinases.
• Mitogen-activated protein kinases (MAPKs) are implicated in this process, but the exact mechanisms and evolutionary conservation are unclear.
• Fission yeast (Schizosaccharomyces pombe) serves as a model for studying conserved eukaryotic cell processes.

Purpose of the Study:

• To investigate the role of MAPKs in regulating anaphase onset in Schizosaccharomyces pombe.
• To elucidate the molecular mechanism by which MAPKs control the anaphase-promoting complex/cyclosome (APC/C).
• To determine if MAPK-dependent mitotic regulation is conserved and functions under stress conditions.

Main Methods:

• Utilized Schizosaccharomyces pombe as a model organism.
• Investigated the interaction and phosphorylation of Slp1Cdc20 by MAPKs, specifically Pmk1.
• Assessed the impact of Pmk1 phosphorylation on Slp1Cdc20 ubiquitylation and degradation.
• Examined the role of Pmk1 in sustaining the spindle assembly checkpoint (SAC) under environmental stress.

Main Results:

• Two MAPKs in S. pombe cooperate to inhibit APC/C activity when the SAC is active.
• The MAPK Pmk1 phosphorylates Slp1Cdc20, the APC/C co-activator, promoting its degradation.
• Pmk1-mediated phosphorylation is essential for maintaining SAC function during environmental stress.
• This contrasts with Cdk1's inability to promote Slp1Cdc20 degradation via phosphorylation.

Conclusions:

• Established a novel mechanism where MAPKs negatively regulate APC/C activity in response to stress stimuli.
• Demonstrated the evolutionary conservation of MAPK-dependent regulation of anaphase entry in eukaryotes.
• Provided a new framework for understanding how stress influences cell cycle progression via MAPK signaling.