Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, 28040 Madrid, Spain.
Int J Mol Sci. 2022 Feb 4;23(3):1791. doi: 10.3390/ijms23031791.
Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention.
暴露于应激环境下的活细胞会引发细胞应答,以保证细胞的最大存活率。这些应答大多数是由丝裂原激活的蛋白激酶(MAPK)级联反应介导的,该级联反应在从酵母到人高度保守。酵母细胞壁损伤条件引发了主要与通过细胞壁完整性(CWI)途径重新编程特定转录应答相关的挽救机制。该途径通过 MAPK Slt2/Mpk1 来协调基因表达的调控,主要通过 Rlm1,在较小程度上通过 SBF(Swi4/Swi6)转录因子。在这篇综述中,我们总结了控制细胞壁应激下基因表达的分子机制,以及染色质结构在这些过程中的作用。这些机制中的一些也在由不同酵母 MAPK 途径控制的其他应激情况下进行了讨论。Slt2 通过与 CWI 反应基因的启动子和编码区的染色质相互作用,来调节转录起始和延伸,但对于 Rlm1 和 SBF 依赖性基因,使用了不同的机制。由于 MAPK 途径在真核细胞中高度保守,并且对控制细胞生理至关重要,因此,提高我们对它们如何调节基因表达的认识可能会影响未来对治疗干预新靶标的识别。