https://www.selleckchem.com/products/cyclo-rgdyk.html Increased macroautophagy/autophagy and lysosomal activity promote tumor growth, survival and chemo-resistance. During acute starvation, autophagy is rapidly engaged by AMPK (AMP-activated protein kinase) activation and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) inhibition to maintain energy homeostasis and cell survival. TFEB (transcription factor E3) and TFE3 (transcription factor binding to IGHM enhancer 3) are master transcriptional regulators of autophagy and lysosomal activity and their cytoplasm/nuclear shuttling is controlled by MTORC1-dependent multisite phosphorylation. However, it is not known whether and how the transcriptional activity of TFEB or TFE3 is regulated. We show that AMPK mediates phosphorylation of TFEB and TFE3 on three serine residues, leading to TFEB and TFE3 transcriptional activity upon nutrient starvation, FLCN (folliculin) depletion and pharmacological manipulation of MTORC1 or AMPK. Collectively, we show that MTORC1 specifically controls TFEB and TFE3 cytomal expression and regulation; DKO double knock-out; DMEM Dulbecco's modified Eagle's medium; DMSO dimethyl sulfoxide; DQ-BSA self-quenched BODIPY® dye conjugates of bovine serum albumin; EBSS Earle's balanced salt solution; FLCN folliculin; GFP green fluorescent protein; GST glutathione S-transferases; HD Huntington disease; HTT huntingtin; KO knock-out; LAMP1 lysosomal associated membrane protein 1; MEF mouse embryonic fibroblasts; MITF melanocyte inducing transcription factor; MTORC1 MTOR complex 1; PolyQ polyglutamine; RPS6 ribosomal protein S6; RT-qPCR reverse transcription quantitative polymerase chain reaction; TCL total cell lysates; TFE3 transcription factor binding to IGHM enhancer 3; TFEB transcription factor EB; TKO triple knock-out; ULK1 unc-51 like autophagy activating kinase 1.COVID-19 is the disease caused by SARS-CoV-2 which has led to 2,643,000 deaths worldwide, a number which is rapidly inc