RT Journal Article T1 MAPK-dependent control of mitotic progression in S. pombe A1 Iglesias Romero, Ana Belén A1 Soto, Teresa A1 Flor-Parra, Ignacio A1 Salas-Pino, Silvia A1 Ruiz Romero, Gabriel A1 Gould, Kathleen L. A1 Cansado. José, A1 Daga, Rafael K1 MAPK, K1 CIP, K1 SAPK, K1 Pmk1, K1 Sty1, K1 Spindle assembly checkpoint, K1 MCC, K1 CDC20/Slp1, K1 APC/C, K1 Osmotic stress, K1 Mitosis, K1 Cytokinesis AB Background Mitogen‑activated protein kinases (MAPKs) preserve cell homeostasis by transducing physicochemical fluctuations of the environment into multiple adaptive responses. These responses involve transcriptional rewiring and the regulation of cell cycle transitions, among others. However, how stress conditions impinge mitotic progres‑sion is largely unknown. The mitotic checkpoint is a surveillance mechanism that inhibits mitotic exit in situations of defective chromosome capture, thus preventing the generation of aneuploidies. In this study, we investigate the role of MAPK Pmk1 in the regulation of mitotic exit upon stress.Results We show that Schizosaccharomyces pombe cells lacking Pmk1, the MAP kinase effector of the cell integrity pathway (CIP), are hypersensitive to microtubule damage and defective in maintaining a metaphase arrest. Epistasis analysis suggests that Pmk1 is involved in maintaining spindle assembly checkpoint (SAC) signaling, and its deletion is additive to the lack of core SAC components such as Mad2 and Mad3. Strikingly, pmk1Δ cells show up to two‑fold increased levels of the anaphase‑promoting complex (APC/C) activator Cdc20Slp1 during unperturbed growth. We demonstrate that Pmk1 physically interacts with Cdc20Slp1 N‑terminus through a canonical MAPK docking site. Most important, the Cdc20 Slp1 pool is rapidly degraded in stressed cells undergoing mitosis through a mechanism that requires MAPK activity, Mad3, and the proteasome, thus resulting in a delayed mitotic exit. Conclusions Our data reveal a novel function of MAPK in preventing mitotic exit and activation of cytokinesis in response to stress. The regulation of Cdc20Slp1 turnover by MAPK Pmk1 provides a key mechanism by which the timing of mitotic exit can be adjusted relative to environmental conditions. PB BMC YR 2024 FD 2024-03-25 LK https://hdl.handle.net/10433/22774 UL https://hdl.handle.net/10433/22774 LA en NO Iglesias-Romero, A. B., Soto, T., Flor-Parra, I., Salas-Pino, S., Ruiz-Romero, G., Gould, K. L., Cansado, J., & Daga, R. R. (2024). MAPK-dependent control of mitotic progression in S. pombe. BMC Biology, 22(1), 71–71. NO PID2021-128408OB-I00 NO FECYT -- ARQUITECTURA Y MECANICA NUCLEAR EN LA LEVADURA DE FISION NO PID2020-112569 GB-I00 NO PY20_00807 NO UPO-1264663 NO R35GM131799 NO Centro Andaluz de Biología del Desarrollo. NO Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia NO Department of Cell and Developmental Biology, Vanderbilt University School of Medicine. DS RIO RD Apr 23, 2026