文章基本信息

标题：The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability
本地全文：下载
作者：Isabel A. Calvo ; Shalini Sharma ; Joao A. Paulo 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：11
页码：1-26
DOI：10.1016/j.isci.2021.103338
语种：English
出版社：Elsevier
摘要：SummaryThe target of Rapamycin complex1 (TORC1) senses and integrates several environmental signals, including amino acid (AA) availability, to regulate cell growth. Folliculin (FLCN) is a tumor suppressor (TS) protein in renal cell carcinoma, which paradoxically activates TORC1 in response to AA supplementation. Few tractable systems for modeling FLCN as a TS are available. Here, we characterize the FLCN-containing complex inSchizosaccharomyces pombe(called BFC) and show that BFC augments TORC1 repression and activation in response to AA starvation and supplementation, respectively. BFC co-immunoprecipitates V-ATPase, a TORC1 modulator, and regulates its activity in an AA-dependent manner. BFC genetic and proteomic networks identify the conserved peptide transmembrane transporter Ptr2 and the phosphoribosylformylglycinamidine synthase Ade3 as new AA-dependent regulators of TORC1. Overall, these data ascribe an additional repressive function to Folliculin in TORC1 regulation and revealS. pombeas an excellent system for modeling the AA-dependent, FLCN-mediated repression of TORC1 in eukaryotes.Graphical abstractDisplay OmittedHighlights•TheS.pombeFolliculin complex, Bhd1-Fnp1 Complex (BFC) augments repression or activation of TORC1 in response to amino acid levels, similar to a rheostat•BFC interacts and regulates V-ATPase activity in response to amino acid levels•Proteomic data reveal Ptr2 and Ade3 as novel amino acid-dependent regulators of TORC1•S. pombeis an excellent model for studying the tumor suppressor function of BFC and related proteinsCellular physiology; Cell biology; Functional aspects of cell biology