mTOR-dependent phosphorylation controls TFEB nuclear export

作者：Napolitano Gennaro; Esposito Alessandra; Choi Heejun; Matarese Maria; Benedetti Valerio; Di Malta Chiara; Monfregola Jlenia; Medina Diego Luis; Lippincott Schwartz Jennifer; Ballabio Andrea^*

来源：Nature Communications, 2018, 9(1): 3312.

DOI：10.1038/s41467-018-05862-6

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.

• 出版日期2018-8-17