The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport

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dc.contributor.authorBustamante, Hianara A.
dc.contributor.authorCereceda, Karina
dc.contributor.authorGonzalez, Alexis E.
dc.contributor.authorValenzuela, Guillermo E.
dc.contributor.authorCheuquemilla, Yorka
dc.contributor.authorHernandez, Sergio
dc.contributor.authorArias-Munoz, Eloisa
dc.contributor.authorCerda-Troncoso, Cristobal
dc.contributor.authorBandau, Susanne
dc.contributor.authorSoza, Andrea
dc.contributor.authorKausel, Gudrun
dc.contributor.authorKerr, Bredford
dc.contributor.authorMardones, Gonzalo A.
dc.contributor.authorCancino, Jorge
dc.contributor.authorHay, Ronald T.
dc.contributor.authorRojas-Fernandez, Alejandro
dc.contributor.authorBurgos, Patricia, V
dc.date.accessioned2025-01-23T19:52:08Z
dc.date.available2025-01-23T19:52:08Z
dc.date.issued2020
dc.description.abstractUbiquitination regulates several biological processes, however the role of specific members of the ubiquitinome on intracellular membrane trafficking is not yet fully understood. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1187 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 regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 with Capzimin (CZM) caused a robust increase in APP levels at the Golgi apparatus and the swelling of this organelle. We showed that this phenotype is the result of rapid inhibition of Golgi-to-ER retrograde transport, a pathway implicated in the early steps of the autophagosomal formation. Indeed, we observed that inhibition of PSMD14 with CZM acts as a potent blocker of macroautophagy by a mechanism related to the retention of Atg9A and Rab1A at the Golgi apparatus. As pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and the K63-Ub chains, act as a crucial regulatory factor for macroautophagy by controlling Golgi-to-ER retrograde transport.
dc.fuente.origenWOS
dc.identifier.doi10.3390/cells9030777
dc.identifier.eissn2073-4409
dc.identifier.urihttps://doi.org/10.3390/cells9030777
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100618
dc.identifier.wosidWOS:000529337400254
dc.issue.numero3
dc.language.isoen
dc.revistaCells
dc.rightsacceso restringido
dc.subjectPSMD14
dc.subjectubiquitin
dc.subjectretrograde
dc.subjecttrafficking
dc.subjectAPP
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport
dc.typeartículo
dc.volumen9
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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