The conserved ATPase Get3/Arr4 modulates the activity of membrane associated proteins in Saccharomyces cerevisiae
The conserved ATPase Get3/Arr4 modulates the activity of membrane associated proteins in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.106.058362
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发表时间：
2006-09-01
期刊：
影响因子：
3.3
通讯作者：
Silver, Pamela A.
中科院分区：
文献类型：
--
作者：
Auld, Kathryn L.;Hitchcock, Amy L.;Silver, Pamela A.
细胞膜动力学的调节对于维持适当的细胞生长和分裂至关重要。Cdc 48-Np 14-Ufd 1复合物是泛素-蛋白酶体系统中几种受调控的膜相关过程所必需的，包括ER相关降解和酵母中脂质组成的控制。在这项研究中，我们报告的结果，在酿酒酵母的温度敏感的np 14等位基因和随后的分析，一个抑制基因，GETS/ARR 4的基因外抑制基因筛选。GET 3基因编码与细菌砷泵的调节组分具有同源性的ATP酶。GET 3的突变体拯救了npl 4突变体的几种表型，并且GETS的转录与蛋白酶体共调节，说明了GETS和NPL 4在泛素-蛋白酶体系统中的功能关系。我们进一步发现，Get 3与跨膜结构域蛋白Get 1/Mdm 39和Get 2/Rmd 7发生生物化学相互作用，并且Delta get 3能够抑制get 1和get 2突变体的表型，包括孢子形成缺陷。结合，我们的GETS与NPL 4，GET 1和GET 2的遗传和生化相互作用的表征暗示Get 3在多个膜依赖性途径。
The regulation of cellular membrane dynamics is crucial for maintaining proper cell growth and division. The Cdc48-Np14-Ufd1 complex is required for several regulated membrane-associated processes as part of the ubiquitin-proteasome system, including ER-associated degradation and the control of lipid composition in yeast. In this study we report the results of a genetic screen in Saccharomyces cerevisiae for extragenic suppressors of a temperature-sensitive npl4 allele and the subsequent analysis of one suppressor, GETS/ARR4. The GET3 gene encodes an ATPase with homology to the regulatory component of the bacterial arsenic pump. Mutants of GET3 rescue several phenotypes of the npl4 mutant and transcription of GETS is coregulated with the proteasome, illustrating a functional relationship between GETS and NPL4 in the ubiquitin-proteasome system. We have further found that Get3 biochemically interacts with the trans-membrane domain proteins Get1/Mdm39 and Get2/Rmd7 and that Delta get3 is able to suppress phenotypes of get1 and get2 mutants, including sporulation defects. In combination, our characterization of GETS genetic and biochemical interactions with NPL4, GET1, and GET2 implicates Get3 in multiple membrane-dependent pathways.