Exploring the ubiquitin-proteasome protein degradation pathway in yeast

2006 ◽  
Vol 34 (6) ◽  
pp. 444-446 ◽  
Author(s):  
Tamara J. Will ◽  
Melissa K. McWatters ◽  
Kristi L. McQuade
Keyword(s):  
Protein Degradation ◽  
Degradation Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Protein

Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway

2005 ◽  
Vol 10 (7) ◽  
pp. 693-704 ◽  
Author(s):  
Naoko Minegishi ◽  
Norio Suzuki ◽  
Yukie Kawatani ◽  
Ritsuko Shimizu ◽  
Masayuki Yamamoto
Keyword(s):  
Protein Degradation ◽  
Degradation Pathway ◽  
Rapid Turnover ◽  
Ubiquitin Proteasome ◽  
Proteasome Protein

Targeting Protein Degradation in Cancer Treatment

2020 ◽  
Vol 14 ◽  
Author(s):  
Imane Bjij ◽  
Ismail Hdoufane ◽  
Mahmoud Soliman ◽  
Menče Najdoska-Bogdanov ◽  
Driss Cherqaoui
Keyword(s):  
Protein Degradation ◽  
Therapeutic Potential ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Cellular Protein ◽  
Cellular Level ◽  
Cancerous Cell ◽  
Promising Target ◽  
Anti Cancer ◽  
Ubiquitin Proteasome

: The ubiquitin proteasome system (UPS) is a crucial protein degradation pathway that involves several enzymes to maintain cellular protein homeostasis. This system has emerged as a major drug target against certain types of cancer as a disruption at the cellular level of UPS enzyme components forces the transformation of normal cell into cancerous cell. Although enormous advancements have been achieved in the understanding of tumorigenesis, efficient cancer therapy remains a goal towards alleviating this serious health issue. Since UPS has become a promising target for anticancer therapies, herein we provide comprehensive review of the ubiquitin proteasome system as a significant process for protein degradation. Herein, the anti-cancer therapeutic potential of this pathway is also discussed.

scholarly journals Assays and technologies for developing proteolysis targeting chimera degraders

2020 ◽  
Author(s):  
Xingui Liu ◽  
Xuan Zhang ◽  
Dongwen Lv ◽  
Yaxia Yuan ◽  
Guangrong Zheng ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Protein Degradation ◽  
Small Molecules ◽  
Rational Design ◽  
Degradation Pathway ◽  
New Techniques ◽  
Design And Optimization ◽  
Structure Activity ◽  
Ubiquitin Proteasome ◽  
Complicated Mechanism

Targeted protein degradation by small-molecule degraders represents an emerging mode of action in drug discovery. Proteolysis targeting chimeras (PROTACs) are small molecules that can recruit an E3 ligase and a protein of interest (POI) into proximity, leading to induced ubiquitination and degradation of the POI by the proteasome system. To date, the design and optimization of PROTACs remain empirical due to the complicated mechanism of induced protein degradation. Nevertheless, it is increasingly appreciated that profiling step-by-step along the ubiquitin-proteasome degradation pathway using biochemical and biophysical assays are essential in understanding the structure–activity relationship and facilitating the rational design of PROTACs. This review aims to summarize these assays and to discuss the potential of expanding the toolbox with other new techniques.

The Ubiquitin-Proteasome System and Memory: Moving Beyond Protein Degradation

2018 ◽  
Vol 24 (6) ◽  
pp. 639-651 ◽  
Author(s):  
Timothy J. Jarome ◽  
Rishi K. Devulapalli
Keyword(s):  
Protein Degradation ◽  
Chromatin Remodeling ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Memory Formation ◽  
Consolidation Process ◽  
Future Studies ◽  
Cellular Models ◽  
Ubiquitin Proteasome

Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation. Despite this evidence, the idea that the UPS is more than a protein degradation pathway has not been examined in the context of memory formation. In this article, we summarize recent findings implicating protein degradation in memory formation and discuss various ways in which both ubiquitin signaling and the proteasome could act independently to regulate epigenetic-mediated transcriptional processes necessary for learning-dependent synaptic plasticity. We conclude by proposing comprehensive models of how non-proteolytic functions of the UPS could work in concert to control epigenetic regulation of the cellular memory consolidation process, which will serve as a framework for future studies examining the role of the UPS in memory formation.

Expression analysis of genes of ubiquitin-proteasome protein degradation system in MPTP-induced mice models of early stages of Parkinson’s disease

2014 ◽  
Vol 456 (1) ◽  
pp. 116-118 ◽  
Author(s):  
E. V. Filatova ◽  
M. I. Shadrina ◽  
A. Kh. Alieva ◽  
A. A. Kolacheva ◽  
P. A. Slominsky ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Degradation ◽  
Expression Analysis ◽  
Early Stages ◽  
Ubiquitin Proteasome ◽  
Proteasome Protein

Ubiquitin-Dependent Proteolysis in Neurons

Physiology ◽  
2003 ◽  
Vol 18 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Lars Klimaschewski
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Degradation ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Present Review ◽  
Major Protein ◽  
Ubiquitin Proteasome ◽  
The Brain

Various studies identified the ubiquitin-proteasome system as the prime suspect in causing neurodegenerative diseases. The present review summarizes our current knowledge about the expression, regulation, and functions of this major protein degradation pathway in the brain, with particular reference to the pathogenesis of associated neurological diseases.

scholarly journals RAPID COMMUNICATION: Residual feed intake in beef cattle is associated with differences in protein turnover and nutrient transporters in ruminal epithelium

2019 ◽  
Vol 97 (5) ◽  
pp. 2181-2187
Author(s):  
Ahmed A Elolimy ◽  
Emad Abdel-Hamied ◽  
Liangyu Hu ◽  
Joshua C McCann ◽  
Daniel W Shike ◽  
...  
Keyword(s):  
Amino Acid ◽  
Beef Cattle ◽  
Protein Degradation ◽  
Insulin Signaling ◽  
Feed Intake ◽  
Feed Efficiency ◽  
Protein Turnover ◽  
Residual Feed Intake ◽  
Ubiquitin Proteasome ◽  
Ruminal Epithelium

Abstract Residual feed intake (RFI) is a widely used measure of feed efficiency in cattle. Although the precise biologic mechanisms associated with improved feed efficiency are not well-known, most-efficient steers (i.e., with low RFI coefficient) downregulate abundance of proteins controlling protein degradation in skeletal muscle. Whether cellular mechanisms controlling protein turnover in ruminal tissue differ by RFI classification is unknown. The aim was to investigate associations between RFI and signaling through the mechanistic target of rapamycin (MTOR) and ubiquitin-proteasome pathways in ruminal epithelium. One hundred and forty-nine Red Angus cattle were allocated to 3 contemporary groups according to sex and herd origin. Animals were offered a finishing diet for 70 d to calculate the RFI coefficient for each. Within each group, the 2 most-efficient (n = 6) and least-efficient animals (n = 6) were selected. Compared with least-efficient animals, the most-efficient animals consumed less feed (P < 0.05; 18.36 vs. 23.39 kg/d DMI). At day 70, plasma samples were collected for insulin concentration analysis. Ruminal epithelium was collected immediately after slaughter to determine abundance and phosphorylation status of 29 proteins associated with MTOR, ubiquitin-proteasome, insulin signaling, and glucose and amino acid transport. Among the proteins involved in cellular protein synthesis, most-efficient animals had lower (P ≤ 0.05) abundance of MTOR, p-MTOR, RPS6KB1, EIF2A, EEF2K, AKT1, and RPS6KB1, whereas MAPK3 tended (P = 0.07) to be lower. In contrast, abundance of p-EEF2K, p-EEF2K:EEF2K, and p-EIF2A:EIF2A in most-efficient animals was greater (P ≤ 0.05). Among proteins catalyzing steps required for protein degradation, the abundance of UBA1, NEDD4, and STUB1 was lower (P ≤ 0.05) and MDM2 tended (P = 0.06) to be lower in most-efficient cattle. Plasma insulin and ruminal epithelium insulin signaling proteins did not differ (P > 0.05) between RFI groups. However, abundance of the insulin-responsive glucose transporter SLC2A4 and the amino acid transporters SLC1A3 and SLC1A5 also was lower (P ≤ 0.05) in most-efficient cattle. Overall, the data indicate that differences in signaling mechanisms controlling protein turnover and nutrient transport in ruminal epithelium are components of feed efficiency in beef cattle.

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