Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway
Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway
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DOI：
10.1128/mcb.25.21.9478-9490.2005
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发表时间：
2005-11-01
影响因子：
5.3
通讯作者：
Maeda, T
中科院分区：
文献类型：
--
作者：
Hayashi, M;Fukuzawa, T;Maeda, T
在许多真菌中，碱性pH的转录反应是由保守的信号转导机制介导的。在酿酒酵母的同源系统中，锌指转录因子Rim 101在碱性条件下被激活以调节靶基因的转录。Rim 101的激活是通过其C-末端抑制结构域的蛋白水解加工来实现的。Rim 101的调节加工需要几种蛋白质，包括钙蛋白酶样蛋白酶Rim 13/Cp 11、推定的蛋白酶支架Rim 20、推定的跨膜蛋白Rim 9和Rim 21/Pal 2以及生化功能未知的Rim 8/Pal 3。为了鉴定新的调节成分，从而确定通路中成分之间的作用顺序，我们筛选了rim 9 Delta和rim 21 Delta突变的抑制因子。三个确定的抑制did 4/vps 2，vps 24和vps 4-都属于“E类”yps突变体，这是常见的缺陷，在多泡体分选。这些突变抑制rim 8、rim 9和rim 21，但不抑制rim 13或rim 20，表明Rim 8、Rim 9和Rim 21在该途径中作用于Rim 13和Rim 20的上游。DID 4、VPS 24或VPS 4本身的破坏将pH传感与Rim 101加工解偶联，导致组成型Rim 101活化。基于广泛的上位性通路激活和失活突变之间的分析，Rim 101通路的架构和调节的模型提出。
In many fungi, transcriptional responses to alkaline pH are mediated by conserved signal transduction machinery. In the homologous system in Saccharomyces cerevisiae, the zinc-finger transcription factor Rim101 is activated under alkaline conditions to regulate transcription of target genes. The activation of Rim101 is exerted through proteolytic processing of its C-terminal inhibitory domain. Regulated processing of Rim101 requires several proteins, including the calpain-like protease Rim13/Cpl1, a putative protease scaffold Rim20, putative transmembrane proteins Rim9, and Rim21/Pal2, and Rim8/Pal3 of unknown biochemical function. To identify new regulatory components and thereby determine the order of action among the components in the pathway, we screened for suppressors of rim9 Delta and rim21 Delta mutations. Three identified suppressors-did4/ vps2, vps24, and vps4-all belonged to "class E" yps mutants, which are commonly defective in multivesicular body sorting. These mutations suppress rim8, rim9, and rim21 but not rim13 or rim20, indicating that Rim8, Rim9, and Rim21 act upstream of Rim13 and Rim20 in the pathway. Disruption of DID4, VPS24, or VPS4, by itself, uncouples pH sensing from Rim101 processing, leading to constitutive Rim101 activation. Based on extensive epistasis analysis between pathway-activating and -inactivating mutations, a model for architecture and regulation of the Rim101 pathway is proposed.