scholarly journals Derailing the UPS of Protein Turnover in Cancer and other Human Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jit Kong Cheong ◽  
Stephen I-Hong Hsu
Keyword(s):  
Protein Turnover ◽  
Cellular Differentiation ◽  
Cell Cycle Control ◽  
Therapeutic Strategies ◽  
Organelle Biogenesis ◽  
Covalent Linkage ◽  
Ubiquitin Proteasome Pathway ◽  
Cellular Processes ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Protein modifications by the covalent linkage of ubiquitin have significant involvement in many cellular processes, including stress response, oncogenesis, viral infection, transcription, protein turnover, organelle biogenesis, DNA repair, cellular differentiation, and cell cycle control. We provide a brief overview of the fundamentals of the regulation of protein turnover by the ubiquitin-proteasome pathway and discuss new therapeutic strategies that aim to mitigate the deleterious effects of its dysregulation in cancer and other human disease pathophysiology.

IGF-I has no effect on postexercise suppression of the ubiquitin-proteasome system in rat skeletal muscle

2002 ◽  
Vol 92 (6) ◽  
pp. 2277-2284 ◽  
Author(s):  
Anthony J. Kee ◽  
Alan J. Taylor ◽  
Anthony R. Carlsson ◽  
Andre Sevette ◽  
Ross C. Smith ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Male Rats ◽  
Ubiquitin Proteasome Pathway ◽  
Muscle Protein Turnover ◽  
Igf I ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Both exercise and insulin-like growth factor I (IGF-I) are known to have major hypertrophic effects in skeletal muscle; however, the interactive effect of exogenous IGF-I and exercise on muscle protein turnover or the ubiquitin-proteasome pathway has not been reported. In the present study, we have examined the interaction between endurance exercise training and IGF-I treatment on muscle protein turnover and the ubiquitin-proteasome pathway in the postexercise period. Adult male rats (270–280 g) were randomized to receive 5 consecutive days of progressive treadmill exercise and/or IGF-I treatment (1 mg · kg body wt−1 · day−1). Twenty-four hours after the last bout of exercise, the rate of protein breakdown in incubated muscles was significantly reduced compared with that in unexercised rats. This was associated with a significant reduction in the chymotrypsin-like activity of the proteasome and the rate of ubiquitin-proteasome-dependent casein hydrolysis in muscle extracts from exercised compared with unexercised rats. In contrast, the muscle expression of the 20S proteasome subunit β-1, ubiquitin, and the 14-kDa E2 ubiquitin-conjugating enzyme was not altered by exercise or IGF-I treatment 24 h postexercise. Exercise had no effect on the rates of total mixed muscle protein synthesis in incubated muscles 24 h postexercise. IGF-I treatment had no effect on muscle weights or the rates of protein turnover 24 h after endurance exercise. These results suggest that a suppression of the ubiquitin-proteasome proteolytic pathway after endurance exercise may contribute to the acute postexercise net protein gain.

Exclusive expression of proteasome subunit β5t in the human thymic cortex

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5186-5191 ◽  
Author(s):  
Utano Tomaru ◽  
Akihiro Ishizu ◽  
Shigeo Murata ◽  
Yukiko Miyatake ◽  
Sayuri Suzuki ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Ubiquitin Proteasome Pathway ◽  
Cellular Processes ◽  
Intracellular Proteins ◽  
Catalytically Active ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Antigen Presenting ◽  
First Time

Abstract The ubiquitin-proteasome pathway, which degrades intracellular proteins, is involved in numerous cellular processes, including the supply of immunocompetent peptides to the antigen presenting machinery. Proteolysis by proteasomes is conducted by three β subunits, β1, β2, and β5, of the 20S proteasome. Recently, a novel β subunit expressed exclusively in cortical thymic epithelial cells was discovered in mice. This subunit, designated β5t, is a component of the thymoproteasome, a specialized type of proteasomes implicated in thymic positive selection. In this study, we show that, like its mouse counterpart, human β5t is expressed exclusively in the thymic cortex. Human β5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells. Human β5t was incorporated into proteasomes with two other catalytically active β subunits β1i and β2i, forming 20S proteasomes with subunit compositions characteristic of thymoproteasomes. The present study demonstrates, for the first time, the existence of thymoproteasomes in the human thymic cortex, indicating that thymoproteasome function is likely conserved between humans and mice.

scholarly journals Proteasome inhibitors: new class of antitumor agents

2003 ◽  
Vol 3 (4) ◽  
pp. 5-10
Author(s):  
Gordan Srkalović
Keyword(s):  
Antitumor Agents ◽  
Proteasome Inhibitors ◽  
26S Proteasome ◽  
Ubiquitin Proteasome Pathway ◽  
Cellular Processes ◽  
New Class ◽  
C Terminus ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

The ubiquitin-proteasome pathway is the principal pathway for intracellular protein degradation1,2 (Fig 1). This pathway selectively degrades an extensive number of short-lived regulatory proteins involved in the control of normal cellular processes. In order to be degraded, proteins targeted by the ubiquitin-proteasome pathway are covalently tagged by polyubiquitination, via a three-step enzymatic process, which ultimately leads to their recognition and degradation, by the 26S proteasome in a highly specific and regulated manner. This process is accomplished by the sequential action of three enzymes: an ATP-dependent ubiquitin-activating enzyme (E1), an ubiquitin-conjugating enzyme (E2) and an ubiquitin-pro-tein ligase (E3).3 This cascade covalently links the C terminus of ubiquitin to a free amino group on the target protein, usually the ε-amino of a lysine residue.

The Ubiquitin-Proteasome Pathway an Emerging Anticancer Strategy for Therapeutics: A Patent Analysis

2015 ◽  
Vol 10 (2) ◽  
pp. 201-213 ◽  
Author(s):  
Chakresh Jain ◽  
Shivam Arora ◽  
Aparna Khanna ◽  
Money Gupta ◽  
Gulshan Wadhwa ◽  
...  
Keyword(s):  
Patent Analysis ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway
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