Inositol Polyphosphate Multikinase Inhibits Liquid-Liquid Phase Separation of TFEB to Negatively Regulate Autophagy Activity.

payth.elady61 shared this article with you from Inoreader Inositol Polyphosphate Multikinase Inhibits Liquid-Liquid Phase Separation of TFEB to Negatively Regulate Autophagy Activity. Via pubmed: autophagy Inositol Polyphosphate Multikinase Inhibits Liquid-Liquid Phase Separation of TFEB to Negatively Regulate Autophagy Activity. Dev Cell. 2020 Dec 07;55(5):588-602.e7 Authors: Chen D, Wang Z, Zhao YG, Zheng H, Zhao H, Liu N, Zhang H Abstract Liquid-liquid phase separation (LLPS) compartmentalizes transcriptional condensates for gene expression, but little is known about how this process is controlled. Here, we showed that depletion of IPMK, encoding inositol polyphosphate multikinase, promotes autophagy and lysosomal function and biogenesis in a TFEB-dependent manner. Cytoplasmic-nuclear trafficking of TFEB, a well-characterized mechanism by which diverse signaling pathways regulate TFEB activity, is not evidently altered by IPMK depletion. We demonstrated that nuclear TFEB forms distinct puncta that colocalize with the Mediator complex and with mRNAs of target lysosomal genes. TFEB undergoes LLPS in vitro. IPMK directly interacts with and inhibits LLPS of TFEB and also dissolves TFEB condensates. Depletion of IPMK increases the number of nuclear TFEB puncta and the co-localization of TFEB with Mediator and mRNAs of target genes. Our study reveals that nuclear-localized IPMK acts as a chaperone to inhibit LL PS of TFEB to negatively control its transcriptional activity. PMID: 33290695 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.