In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome

Molecular Cell
Hikaru TsuchiyaYasushi Saeki

Abstract

Ubiquitin-binding domain (UBD) proteins regulate numerous cellular processes, but their specificities toward ubiquitin chain types in cells remain obscure. Here, we perform a quantitative proteomic analysis of ubiquitin linkage-type selectivity of 14 UBD proteins and the proteasome in yeast. We find that K48-linked chains are directed to proteasomal degradation through selectivity of the Cdc48 cofactor Npl4. Mutating Cdc48 results in decreased selectivity, and lacking Rad23/Dsk2 abolishes interactions between ubiquitylated substrates and the proteasome. Among them, only Npl4 has K48 chain specificity in vitro. Thus, the Cdc48 complex functions as a K48 linkage-specifying factor upstream of Rad23/Dsk2 for proteasomal degradation. On the other hand, K63 chains are utilized in endocytic pathways, whereas both K48 and K63 chains are found in the MVB and autophagic pathways. Collectively, our results provide an overall picture of the ubiquitin network via UBD proteins and identify the Cdc48-Rad23/Dsk2 axis as a major route to the proteasome.

Associated Datasets

May 31, 2017·Hikaru Tsuchiya

Citations

Jan 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Fumiaki OhtakeKeiji Tanaka
Sep 12, 2018·The Journal of Clinical Investigation·Chengjun HuXuejun Wang
Feb 8, 2018·Nature Communications·Hikaru TsuchiyaYasushi Saeki
Apr 14, 2018·Annual Review of Biochemistry·Jared A M BardAndreas Martin
May 11, 2019·Protein Science : a Publication of the Protein Society·Takuya Tomita, Andreas Matouschek
Apr 19, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chunjie ShengShuai Chen
Mar 12, 2020·Molecular Biology of the Cell·Stephen D WillisKatrina F Cooper
Jun 23, 2020·Annual Review of Biochemistry·Cole S Sitron, Onn Brandman
Jan 26, 2020·Nature Communications·Kirby Martinez-FontsAndreas Matouschek
Mar 3, 2020·ELife·Meredith B MetzgerAllan M Weissman
Jun 27, 2020·Pharmaceuticals·Hikaru TsuchiyaYasushi Saeki
Sep 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Donghoon LeeAlfred L Goldberg
Mar 6, 2019·Cold Spring Harbor Perspectives in Biology·Daniel Finley, Miguel A Prado
Apr 4, 2019·Nature Reviews. Molecular Cell Biology·Claudio A P Joazeiro
Jun 25, 2019·Frontiers in Molecular Biosciences·Richard S Marshall, Richard D Vierstra
Mar 8, 2020·Nature Communications·Atsuya NishiyamaMakoto Nakanishi
Jul 4, 2018·Nature Structural & Molecular Biology·Nicholas O BodnarTom A Rapoport
Nov 30, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hyoung Tae Kim, Alfred L Goldberg
Dec 15, 2019·Nature Communications·Yusuke SatoShuya Fukai
Jun 3, 2020·Nature Chemical Biology·Emma C CarrollSusan Marqusee
Aug 25, 2019·Biomolecules·Bernat Coll-Martínez, Bernat Crosas
Feb 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Galen A Collins, Alfred L Goldberg
Dec 6, 2020·The Journal of Biological Chemistry·Alexandra M WhiteleyDaniel Finley
Jan 1, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Oct 16, 2020·Science Advances·Alexander JussupowCarlo Camilloni
Jan 8, 2021·Biomolecules·Dina FranićMirta Boban
Jan 20, 2020·Biochemical and Biophysical Research Communications·Md Tanvir IslamMasatoshi Esaki
Jan 12, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Apr 16, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Apr 20, 2021·Environmental Microbiology Reports·Dingyi WangFuzhong Wu
May 17, 2021·Drug Discovery Today·Zheng-Qing LiYing Wang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.