mTOR-dependent phosphorylation controls TFEB nuclear export.
mTOR-dependent phosphorylation controls TFEB nuclear export.
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DOI：
10.1038/s41467-018-05862-6
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发表时间：
2018-08-17
影响因子：
16.6
通讯作者：
Ballabio A
中科院分区：
文献类型：
--
作者：
Napolitano G;Esposito A;Choi H;Matarese M;Benedetti V;Di Malta C;Monfregola J;Medina DL;Lippincott-Schwartz J;Ballabio A
在饥饿期间，分解代谢过程的转录激活由核转位和随后的转录因子EB（TFEB）（自噬和溶酶体生物发生的主调节剂）的激活诱导。然而，TFEB如何在营养物再喂养时失活目前尚不清楚。在这里，我们表明，TFEB亚细胞定位动态控制其连续穿梭之间的细胞质和细胞核，与核出口代表一个限制步骤。TFEB核输出由CRM 1介导，并通过丝氨酸S142和S138的mTOR依赖性分级多位点磷酸化（位于核输出信号（内斯）附近）由营养物质可用性调节。我们关于TFEB核质穿梭的数据表明mTOR在核输出中的不可预测的作用。在氨基酸剥夺时，TFEB从细胞质易位到细胞核。在这里，作者确定了TFEB中的核输出信号，该信号被输出蛋白CRM 1识别，并表明mTOR在S142和S138处的双重磷酸化加速了TFEB的输出。
During starvation the transcriptional activation of catabolic processes is induced by the nuclear translocation and consequent activation of transcription factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis. However, how TFEB is inactivated upon nutrient refeeding is currently unknown. Here we show that TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step. TFEB nuclear export is mediated by CRM1 and is modulated by nutrient availability via mTOR-dependent hierarchical multisite phosphorylation of serines S142 and S138, which are localized in proximity of a nuclear export signal (NES). Our data on TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of mTOR in nuclear export. On amino acid deprivation TFEB translocates from the cytoplasm to the nucleus. Here the authors identify a nuclear export signal in TFEB that is recognized by the exportin CRM1, and show that dual phosphorylation at S142 and S138 by mTOR accelerates export of TFEB.
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影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
21.3
作者：
Medina DL;Di Paola S;Peluso I;Armani A;De Stefani D;Venditti R;Montefusco S;Scotto-Rosato A;Prezioso C;Forrester A;Settembre C;Wang W;Gao Q;Xu H;Sandri M;Rizzuto R;De Matteis MA;Ballabio A
通讯作者：
Ballabio A
影响因子：
16.6
作者：
Chauhan S;Ahmed Z;Bradfute SB;Arko-Mensah J;Mandell MA;Won Choi S;Kimura T;Blanchet F;Waller A;Mudd MH;Jiang S;Sklar L;Timmins GS;Maphis N;Bhaskar K;Piguet V;Deretic V
通讯作者：
Deretic V
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
3.5
作者：
Song, Wensi;Wang, Fan;Segatori, Laura
通讯作者：
Segatori, Laura