The fission yeast MAPK Spc1 senses perturbations in Cdc25 and Wee1 activities and targets Rad24 to restore this balance

Abstract

Mitogen-activated protein kinases (MAPKs) play vital roles in multiple cellular processes and represent prominently pursued targets for development of therapeutic regimes. The MAPK Spc1 (p38 homologue) is known to be very important for both mitotic promotion and delay in Schizosaccharomyces pombe. However, the mechanism responsible for mitotic inhibition has remained elusive. Cdc25 (Cdc2 activator) and Wee1 (Cdc2 inhibtor) are important determinants of mitotic timing in all eukaryotes. Our results show that Spc1 can sense the perturbations in the balance of Cdc25 and Wee1 activities in S. pombe and that its function as a mitotic inhibitor is very important for controlling the same. An Spc1-Srk1-Rad24-dependent pathway for mitotic inhibition has been reported earlier.Here we report the presence of an alternative mechanism wherein Spc1 targets the 14-3-3 protein, Rad24, independently of Srk1, leading to relocalization of Cdc25 and mitotic inhibition. Our observations suggest that this pathway can serve as a backup mechanism for Cdc2 inactivation in the absence of Wee1.

Keywords: Cdc2; Cdc25; Rad24; S. Pombe; Spc1; Wee1; mitosis.