Bauer Justin R, Robinson Tamaraty L, Strich Randy, Cooper Katrina F
Department of Cell and Molecular Biology, School of Osteopathic Medicine, Rowan-Virtua College of Medicine and Life Sciences, Rowan University, Stratford, NJ 08084, USA.
Cells. 2025 Apr 25;14(9):636. doi: 10.3390/cells14090636.
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.
在受到不利的环境信号刺激后，细胞会对调控转录、翻译和蛋白质降解系统的信号通路进行重编程。这种重编程对于恢复体内平衡或促使细胞死亡至关重要。本综述聚焦于两种核转录调节因子细胞周期蛋白C（cyclin C）和Med13的次要作用，它们在这一决策过程中发挥关键作用。这两种蛋白质都是中介体复合物的中介体激酶模块（MKM）的成员，在正常生理条件下，该模块对一部分应激反应基因进行正向和负向调节。然而，细胞周期蛋白C和Med13会在细胞死亡或细胞存活信号刺激后转移至细胞质中，分别与大量细胞死亡和细胞存活蛋白相互作用。在细胞质中，细胞周期蛋白C是应激诱导的线粒体过度分裂所必需的，并促进程序性细胞死亡途径。细胞质中的Med13会刺激应激诱导的加工小体（P小体）组装，并且通过货物搭便车自噬对一部分P小体组装因子进行自噬降解是必需的。本综述聚焦于细胞周期蛋白C和Med13的这些次要作用，即所谓的“夜间工作”，概述了这些次要功能在应激后维持细胞内稳态中的重要性。
