scholarly journals Inverse Correlation Between MPSR1 E3 Ubiquitin Ligase and HSP90.1 Balances Cytoplasmic Protein Quality Control

2019 ◽  
Vol 180 (2) ◽  
pp. 1230-1240 ◽  
Author(s):  
Jong Hum Kim ◽  
Tae Rin Oh ◽  
Seok Keun Cho ◽  
Seong Wook Yang ◽  
Woo Taek Kim
Keyword(s):  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
E3 Ubiquitin Ligase ◽  
Protein Quality Control ◽  
Inverse Correlation ◽  
Cytoplasmic Protein

scholarly journals The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation

2017 ◽  
Vol 28 (9) ◽  
pp. 1165-1176 ◽  
Author(s):  
Quentin Defenouillère ◽  
Abdelkader Namane ◽  
John Mouaikel ◽  
Alain Jacquier ◽  
Micheline Fromont-Racine
Keyword(s):  
Quality Control ◽  
Protein Aggregation ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
Translation Termination ◽  
E3 Ubiquitin Ligase ◽  
Protein Quality Control ◽  
Control Mechanisms ◽  
Ubiquitin Ligase Activity ◽  
Control Complex

Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the ribosome-bound quality control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfunction in translation termination. The RQC complex polyubiquitylates aberrant polypeptides and recruits a Cdc48 hexamer to extract them from 60S particles in order to escort them to the proteasome for degradation. Whereas the steps from stalled 60S recognition to aberrant peptide polyubiquitylation by the RQC complex have been described, the mechanism leading to proteasomal degradation of these defective translation products remains unknown. We show here that the RQC complex also exists as a ribosome-unbound complex during the escort of aberrant peptides to the proteasome. In addition, we identify a new partner of this light version of the RQC complex, the E3 ubiquitin ligase Tom1. Tom1 interacts with aberrant nascent peptides and is essential to limit their accumulation and aggregation in the absence of Rqc1; however, its E3 ubiquitin ligase activity is not required. Taken together, these results reveal new roles for Tom1 in protein quality control, aggregate prevention, and, therefore, proteostasis maintenance.

scholarly journals Role of a ribosome-associated E3 ubiquitin ligase in protein quality control

Nature ◽  
2010 ◽  
Vol 467 (7314) ◽  
pp. 470-473 ◽  
Author(s):  
Mario H. Bengtson ◽  
Claudio A. P. Joazeiro
Keyword(s):  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
E3 Ubiquitin Ligase ◽  
Protein Quality Control

scholarly journals Coupled protein quality control during nonsense mediated mRNA decay

2021 ◽  
Author(s):  
Alison J Inglis ◽  
Alina Guna ◽  
Angel Galvez Merchan ◽  
Akshaye Pal ◽  
Theodore K Esantsi ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Mrna Degradation ◽  
Protein Product ◽  
Reporter System

Translation of mRNAs containing premature termination codons (PTCs) can result in truncated protein products with deleterious effects. Nonsense-mediated decay (NMD) is a surveillance path-way responsible for detecting and degrading PTC containing transcripts. While the molecular mechanisms governing mRNA degradation have been extensively studied, the fate of the nascent protein product remains largely uncharacterized. Here, we use a fluorescent reporter system in mammalian cells to reveal a selective degradation pathway specifically targeting the protein product of an NMD mRNA. We show that this process is post-translational, and dependent on an intact ubiquitin proteasome system. To systematically uncover factors involved in NMD-linked protein quality control, we conducted genome-wide flow cytometry-based screens. Our screens recovered known NMD factors, and suggested a lack of dependence on the canonical ribosome-quality control (RQC) pathway. Finally, one of the strongest hits in our screens was the E3 ubiquitin ligase CNOT4, a member of the CCR4-NOT complex, which is involved in initiating mRNA degradation. We show that CNOT4 is involved in NMD coupled protein degradation, and its role depends on a functional RING ubiquitin ligase domain. Our results demonstrate the existence of a targeted pathway for nascent protein degradation from PTC containing mRNAs, and provide a framework for identifying and characterizing factors involved in this process.

scholarly journals Loss of protein quality control gene UBR1 sensitizes Saccharomyces cerevisiae to the aminoglycoside hygromycin B

Fine Focus ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. 76-83
Author(s):  
Avery M. Runnebohm ◽  
Melissa D. Evans ◽  
Adam E. Richardson ◽  
Samantha M. Turk ◽  
James B. Olesen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Eukaryotic Cells ◽  
Hygromycin B ◽  
Eukaryotic Microorganism ◽  
Human Enzyme ◽  
A Site

Ubr1 is a conserved ubiquitin ligase involved in the degradation of aberrant proteins in eukaryotic cells. The human enzyme is found mutated in patients with Johanson-Blizzard syndrome. We hypothesized that Ubr1 is necessary for optimal cellular fitness in conditions associated with elevated abundance of aberrant and misfolded proteins. Indeed, we found that loss of Ubr1 in the model eukaryotic microorganism Saccharomyces cerevisiae strongly sensitizes cells to hygromycin B, which reduces translational fidelity by causing ribosome A site distortion. Our results are consistent with a prominent role for Ubr1 in protein quality control. We speculate that disease manifestations in patients with Johanson-Blizzard syndrome are linked, at least in part, to defects in protein quality control caused by loss of Ubr1 function.

scholarly journals CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding

Science ◽  
2015 ◽  
Vol 349 (6243) ◽  
pp. 91-95 ◽  
Author(s):  
Hsiu-Chuan Lin ◽  
Szu-Chi Ho ◽  
Yi-Yun Chen ◽  
Kay-Hooi Khoo ◽  
Pang-Hung Hsu ◽  
...  
Keyword(s):  
Quality Control ◽  
Control System ◽  
Protein Degradation ◽  
Genetic Code ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
Translation Termination ◽  
Protein Quality Control ◽  
Selenium Intake ◽  
Protein Quality Control System

Selenocysteine (Sec) is translated from the codon UGA, typically a termination signal. Codon duality extends the genetic code; however, the coexistence of two competing UGA-decoding mechanisms immediately compromises proteome fidelity. Selenium availability tunes the reassignment of UGA to Sec. We report a CRL2 ubiquitin ligase–mediated protein quality-control system that specifically eliminates truncated proteins that result from reassignment failures. Exposing the peptide immediately N-terminal to Sec, a CRL2 recognition degron, promotes protein degradation. Sec incorporation destroys the degron, protecting read-through proteins from detection by CRL2. Our findings reveal a coupling between directed translation termination and proteolysis-assisted protein quality control, as well as a cellular strategy to cope with fluctuations in organismal selenium intake.

scholarly journals The San1 Ubiquitin Ligase Functions Preferentially with Ubiquitin-conjugating Enzyme Ubc1 during Protein Quality Control

2016 ◽  
Vol 291 (36) ◽  
pp. 18778-18790 ◽  
Author(s):  
Rebeca Ibarra ◽  
Daniella Sandoval ◽  
Eric K. Fredrickson ◽  
Richard G. Gardner ◽  
Gary Kleiger
Keyword(s):  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

scholarly journals Ubiquitin Ligase Redundancy and Nuclear-Cytoplasmic Localization in Yeast Protein Quality Control

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1821
Author(s):  
Carolyn Allain Breckel ◽  
Mark Hochstrasser
Keyword(s):  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
Three Dimensional ◽  
Protein Quality Control ◽  
Ubiquitin Ligases ◽  
Ubiquitin Proteasome System ◽  
Current Evidence ◽  
Cellular Processes ◽  
Cellular Compartments

The diverse functions of proteins depend on their proper three-dimensional folding and assembly. Misfolded cellular proteins can potentially harm cells by forming aggregates in their resident compartments that can interfere with vital cellular processes or sequester important factors. Protein quality control (PQC) pathways are responsible for the repair or destruction of these abnormal proteins. Most commonly, the ubiquitin-proteasome system (UPS) is employed to recognize and degrade those proteins that cannot be refolded by molecular chaperones. Misfolded substrates are ubiquitylated by a subset of ubiquitin ligases (also called E3s) that operate in different cellular compartments. Recent research in Saccharomyces cerevisiae has shown that the most prominent ligases mediating cytoplasmic and nuclear PQC have overlapping yet distinct substrate specificities. Many substrates have been characterized that can be targeted by more than one ubiquitin ligase depending on their localization, and cytoplasmic PQC substrates can be directed to the nucleus for ubiquitylation and degradation. Here, we review some of the major yeast PQC ubiquitin ligases operating in the nucleus and cytoplasm, as well as current evidence indicating how these ligases can often function redundantly toward substrates in these compartments.

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