Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins

Nadinath B Nillegoda; Maria A Theodoraki; Atin K Mandal; Katie J Mayo; Hong Yu Ren; Rasheda Sultana; Kenneth Wu; Jill Johnson; Douglas M Cyr; Avrom J Caplan

doi:10.1091/mbc.E10-02-0098

Back

Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins

Journal article

Open access

Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins

Nadinath B Nillegoda, Maria A Theodoraki, Atin K Mandal, Katie J Mayo, Hong Yu Ren, Rasheda Sultana, Kenneth Wu, Jill Johnson, Douglas M Cyr and Avrom J Caplan

Molecular biology of the cell, Vol.21(13), pp.2102-2116

07/01/2010

DOI: https://doi.org/10.1091/mbc.E10-02-0098

Handle:

https://hdl.handle.net/2376/114959

PMCID: PMC2893976

PMID: 20462952

Files and links (1)

url

https://doi.org/10.1091/mbc.E10-02-0098View

Published (Version of record) Open

Abstract

Cyclic AMP-Dependent Protein Kinases - metabolism

Peptides - chemistry

Ubiquitin-Protein Ligases - metabolism

Saccharomyces cerevisiae Proteins - genetics

Ubiquitin-Protein Ligases - chemistry

Protein Folding

HSP70 Heat-Shock Proteins - metabolism

Saccharomyces cerevisiae - metabolism

Ubiquitination

Animals

Cyclic AMP-Dependent Protein Kinases - genetics

Peptides - metabolism

Protein Denaturation

Saccharomyces cerevisiae Proteins - metabolism

Protein Conformation

Proteasome Endopeptidase Complex - metabolism

Proteasome Inhibitors

Ubiquitin-Protein Ligases - genetics

Unfolded Protein Response - physiology

Luciferases, Firefly - metabolism

Saccharomyces cerevisiae Proteins - chemistry

Quality control systems facilitate polypeptide folding and degradation to maintain protein homeostasis. Molecular chaperones promote folding, whereas the ubiquitin/proteasome system mediates degradation. We show here that Saccharomyces cerevisiae Ubr1 and Ubr2 ubiquitin ligases promote degradation of unfolded or misfolded cytosolic polypeptides. Ubr1 also catalyzes ubiquitinylation of denatured but not native luciferase in a purified system. This activity is based on the direct interaction of denatured luciferase with Ubr1, although Hsp70 stimulates polyubiquitinylation of the denatured substrate. We also report that loss of Ubr1 and Ubr2 function suppressed the growth arrest phenotype resulting from chaperone mutation. This correlates with increased protein kinase maturation and indicates partitioning of foldable conformers toward the proteasome. Our findings, based on the efficiency of this quality control system, suggest that the cell trades growth potential to avert the potential toxicity associated with accumulation of unfolded or misfolded proteins. Ubr1 and Ubr2 therefore represent E3 components of a novel quality control pathway for proteins synthesized on cytosolic ribosomes.

Metrics

5 Record Views

Details

Title: Ubr1 and Ubr2 function in a quality control pathway for degradation of unfolded cytosolic proteins
Creators: Nadinath B Nillegoda - Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA
Maria A Theodoraki
Atin K Mandal
Katie J Mayo
Hong Yu Ren
Rasheda Sultana
Kenneth Wu
Jill Johnson
Douglas M Cyr
Avrom J Caplan
Publication Details: Molecular biology of the cell, Vol.21(13), pp.2102-2116
Academic Unit: UNKNOWN
Publisher: United States
Grant note: R01GM70596 / NIGMS NIH HHS R01 GM067785 / NIGMS NIH HHS U54CA132378 / NCI NIH HHS G12 RR003060 / NCRR NIH HHS 5G12-RR03060 / NCRR NIH HHS U54 CA132378 / NCI NIH HHS R01GM067785 / NIGMS NIH HHS R01 GM070596 / NIGMS NIH HHS
Identifiers: 99900547786001842
Language: English
Resource Type: Journal article