Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED) and Departament de Bioquímica i Biologia Molecular, Universitat de València, 46100 Burjassot (Valencia), Spain.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.
J Cell Sci. 2020 Dec 21;133(24):jcs251413. doi: 10.1242/jcs.251413.
Start is the main decision point in the eukaryotic cell cycle at which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional programme through the inactivation of Start transcriptional repressors: the retinoblastoma family in mammals, or Whi5 and its recently identified paralogue Whi7 (also known as Srl3) in budding yeast. Here, we provide a comprehensive comparison of Whi5 and Whi7 that reveals significant qualitative differences. Indeed, the expression, subcellular localization and functionality of Whi7 and Whi5 are differentially regulated. Importantly, Whi7 shows specific properties in its association with promoters not shared by Whi5, and for the first time, we demonstrate that Whi7, and not Whi5, can be the main contributor to Start inhibition such as it occurs in the response to cell wall stress. Our results help to improve understanding of the interplay between multiple differentially regulated Start repressors in order to face specific cellular conditions.
起始点是真核细胞周期中的主要决策点，细胞在此决定是否开始新一轮的细胞分裂。这涉及通过失活起始转录抑制剂来不可逆地激活转录程序：哺乳动物中的视网膜母细胞瘤家族，或芽殖酵母中的 Whi5 及其最近发现的同源物 Whi7（也称为 Srl3）。在这里，我们对 Whi5 和 Whi7 进行了全面比较，揭示了显著的定性差异。事实上，Whi7 的表达、亚细胞定位和功能受到不同的调节。重要的是，Whi7 与启动子的结合具有 Whi5 所没有的特定特性，而且我们首次证明，Whi7 而不是 Whi5 可以成为起始抑制的主要贡献者，例如在应对细胞壁应激时。我们的研究结果有助于更好地理解多个差异调节的起始抑制剂之间的相互作用，以应对特定的细胞条件。
