The ubiquitin–proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34. We find that this ubiquitination enhances the binding of VPS34 to proteasomes for degradation, thereby suppressing autophagosome formation and maturation. Under ER and proteotoxic stresses, UBE3C recruitment to phagophores is compromised with a concomitant increase of its association with proteasomes. This switch attenuates the action of UBE3C on VPS34, thereby elevating autophagy activity to facilitate proteostasis, ER quality control and cell survival. Specifically in the liver, we show that TRABID-mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis. This study identifies a ubiquitination type on VPS34 and elucidates its cellular fate and physiological functions in proteostasis and liver metabolism.
Herein, we propose a novel approach for area-selective tunable growth of uniform monolayer or bilayer WS 2 on dielectric substrates through in situ conversion of a predeposited W metal pad to WO x initially and then to WS 2 mono-and bilayers. Compared with the various transfer methods that have been used previously for multilayer stacking, this direct-growth method has the advantages of producing cleaner interfaces and the capability of growing tunable layers on target substrates, thereby making it more suitable for manufacturing processes. The WS 2 bilayer displayed uniform optical properties, with the atomic arrangement between layers having an AA stacking order that are supposed to have higher mobility. We adopted these WS 2 monolayers and bilayers in fieldeffect transistors. Accordingly, this approach for highly area-selective growth of transition metal dichalcogenide monolayers and bilayers with metal pads and their in situ conversion appears to provide effective platforms for further device applications.
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