Jan 30, 2020

The proteasomal deubiquitinating enzyme PSMD14 regulates macroautophagy by controlling Golgi-to-ER retrograde transport

BioRxiv : the Preprint Server for Biology
Hianara BustamantePatricia Burgos


Ubiquitination regulates several biological processes. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1,187 genes of the human "ubiquitinome" using Amyloid Precursor Protein (APP) as a reporter. We identified the deubiquitinating enzyme PSMD14, a subunit of the 19S regulatory particle of the proteasome, specific for K63-Ub chains in cells, as a novel key regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 caused a robust and rapid inhibition of Golgi-to-ER retrograde transport which leads to a potent blockage of macroautophagy by a mechanism associated with the retention of Atg9A and Rab1A at the Golgi apparatus. Because pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and their K-63-Ub chains, act as a crucial regulator factor for macroautophagy by controlling Golgi-to-ER retrograde transport. Keywords: PSMD14, Ubiquitin, Retrograde, Trafficking, APP

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Mentioned in this Paper

Ubiquitinated Proteins
Regulation of Macroautophagy
PA700 Regulatory Module
Membrane Protein Traffic
Rab1A GTP-Binding Protein
PSMD14 protein, human
Ubiquitination Regulation Protein

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