Dual Function of USP14 Deubiquitinase in Cellular Proteasomal Activity and Autophagic Flux

Cell Reports
Eunkyoung KimMin Jae Lee

Abstract

The ubiquitin-proteasome system and the autophagy-lysosome system are two major intracellular proteolytic pathways in eukaryotes. Although several biochemical mechanisms underlying the crosstalk between them have been suggested, little is known about the effect of enhanced proteasome activity on autophagic flux. Here, we found that upregulation of proteasome activity, which was achieved through the inhibition of USP14, significantly impaired cellular autophagic flux, especially at the autophagosome-lysosome fusion step. UVRAG appeared to function as a crucial checkpoint for the proper progression of autophagic flux. Although proteasome activation through USP14 inhibition facilitated the clearance of microtubule-associated protein tau (MAPT) and reduced the amount of its oligomeric forms, the same conditions increased the formation of inclusion bodies from nonproteasomal substrates such as huntingtin with long polyglutamine repeats. Our results collectively indicate that USP14 may function as a common denominator in the compensatory negative feedback between the two major proteolytic processes in the cell.

Citations

Apr 17, 2019·Protein Engineering, Design & Selection : PEDS·Wenting ZhaoLaura Segatori
Jul 13, 2019·International Journal of Molecular Sciences·Nicolas AlbornozPatricia Burgos
Dec 19, 2019·Frontiers in Oncology·Xing-Wei NanXiao-Jian Yan
Jun 18, 2020·International Journal of Molecular Sciences·Tamás Csizmadia, Péter Lőw
Sep 6, 2020·Cells·Zhangyuan YinDaniel J Klionsky
Sep 22, 2020·Journal of Alzheimer's Disease : JAD·Yejin YunYoung Ho Kim
Oct 28, 2019·International Journal of Molecular Sciences·Kyung Ho HanPeter Chang-Whan Lee
Jun 26, 2020·Frontiers in Physiology·Joy Chakraborty, Elena Ziviani
Jul 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Won Hoon ChoiMin Jae Lee
Oct 7, 2020·Cells·Yohannes Afework MebratuYohannes Tesfaigzi
Apr 30, 2020·International Journal of Molecular Sciences·Fiona LimanaqiFrancesco Fornai
Jan 9, 2021·Cell Death and Differentiation·Marlene F SchmidtGrant Dewson
Feb 13, 2021·Acta Tropica·Andressa Barban do PatrocínioVanderlei Rodrigues
Oct 29, 2020·Genes & Genomics·Garbin Yu, Seogang Hyun
Mar 7, 2019·Journal of Medicinal Chemistry·Evert Njomen, Jetze J Tepe

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.