Isc10, an Inhibitor That Links the Anaphase-Promoting Complex to a Meiosis-Specific Mitogen-Activated Protein Kinase.

Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in yeast that controls spore differentiation. It is activated by a MAPK binding protein, Ssp2, upon completion of the meiotic divisions. The activation of Smk1 by Ssp2 is positively regulated by a meiosis-specific coactivator of the anaphase promoting complex (APC/C) E3 ubiquitin ligase, Ama1. Here, we identify Isc10 as an inhibitor that links APC/C to Smk1 activation. Isc10 and Smk1 form an inhibited complex during meiosis I (MI). Ssp2 is produced later in the program, and it forms a ternary complex with Isc10 and Smk1 during MII that is poised for activation. Upon completion of MII, Isc10 is ubiquitylated and degraded in an -dependent manner, thereby triggering the activation of Smk1 by Ssp2. Mutations that caused Ssp2 to be produced before MII, or Δ mutations, modestly reduced the efficiency of spore differentiation whereas spores were nearly absent in the double mutant. These findings define a pathway that couples spore differentiation to the G-like phase of the cell cycle.