Quitting Your Day Job in Response to Stress: Cell Survival and Cell Death Require Secondary Cytoplasmic Roles of Cyclin C and Med13

Following unfavorable environmental cues, cells reprogram pathways that govern transcription, translation, and protein degradation systems. This reprogramming is essential to restore homeostasis or commit to cell death. This review focuses on the secondary roles of two nuclear transcriptional regulators, cyclin C and Med13, which play key roles in this decision process. Both proteins are members of the Mediator kinase module (MKM) of the Mediator complex, which, under normal physiological conditions, positively and negatively regulates a subset of stress response genes. However, cyclin C and Med13 translocate to the cytoplasm following cell death or cell survival cues, interacting with a host of cell death and cell survival proteins, respectively. In the cytoplasm, cyclin C is required for stress-induced mitochondrial hyperfission and promotes regulated cell death pathways. Cytoplasmic Med13 stimulates the stress-induced assembly of processing bodies (P-bodies) and is required for the autophagic degradation of a subset of P-body assembly factors by cargo hitchhiking autophagy. This review focuses on these secondary, a.k.a. “night jobs” of cyclin C and Med13, outlining the importance of these secondary functions in maintaining cellular homeostasis following stress.