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Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
Signal transduction pathways also regulate the lifespan of proteins by controlling their degradation rate. Protein degradation can occur via at least three processes: ubiquitin-proteasome system;autophagy-lysosomal pathways and/orcytosolic proteolytic systems.
Modulating Cytolytic Responses to Infectious Pathogens
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Rebecca Pogue Caley, Jeffrey A. Frelinger
Major histocompatibility complex class I restricted antigen presentation primarily involves the MHC class I heavy chain binding peptides which have been generated within the cytoplasm of the cell. Several lines of evidence implicate the proteasome as involved in this degradation of cytosolic proteins for antigen presentation. First, genes encoding for two of the proteasome’s subunits, low-molecular-weight protein (LMP)-2 and LMP-7, are located within the MHC class II region [2,3]. Second, the proteasome is involved in both ubiquitin-dependent and ubiquitin-independent protein degradation pathways within the cell. Third, inhibitors of proteasome function, such as dipeptide aldehydes, can block the presentation of model peptides [4].
Proteasome and Protease Inhibitors
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
N. E. Franke, J. Vink, J. Cloos, Gertjan J. L. Kaspers
More than 80% of all eukaryotic protein degradation is controlled by the ubiquitin-proteasome pathway (23). This pathway regulates protein ubiquitination, and subsequent recognition and degradation by the proteasome (Fig. 1).
Circadian regulation of cardiac muscle function and protein degradation
Published in Chronobiology International, 2023
Proteostasis, including protein synthesis, processing/folding and degradation, is an important cellular mechanism in cardiac muscles (Henning and Brundel 2017; McLendon and Robbins 2015). Compared with non-muscle cells, cardiac muscles are terminally differentiated, must contract throughout lifetime, require robust metabolic/stress responses and involve specialized cellular machineries for electric conductance. The structural and functional unit of striated muscles, including both cardiac and skeletal muscles, is the sarcomere (Martin and Kirk 2020; Ono 2010), which is highly conserved throughout from worms to mammals. Sarcomeres line up sequentially, and tied together by a complex protein assembly called Z-disc to form contractible myofibrils, which in turn are bound in bundles to form cardiomyocytes. The sarcomere consists mainly of the myosin thick filaments and actin thin filaments, with a large number of associated structural and regulatory proteins. Given the heart is the first organ to be formed after birth and must continuously function until death, and that cardiomyocytes are post-mitotic, protein quality control at the sarcomere plays a particularly important role in cardiac proteostasis (Henning and Brundel 2017; Martin and Kirk 2020). Of particular importance is protein degradation mechanisms to remove misfolded or faulty proteins.
The discovery and design of novel HIV-1 capsid modulators and future perspectives
Published in Expert Opinion on Drug Discovery, 2023
Dang Ding, Shujing Xu, Xujie Zhang, Xiangyi Jiang, Simon Cocklin, Alexej Dick, Peng Zhan, Xinyong Liu
In addition, targeted protein degradation has opened up a new field of drug discovery in recent years by utilizing an alternative pharmacological strategy [62]. Importantly, it has exciting advantages promoting its application, such as a wide range of targets, small dosage, and minimal catalyst required. Targeted protein degradation can be accomplished by developing bifunctional compounds commonly known as proteolysis-targeting chimeras (PROTACs) [63]. This strategy has been successfully applied in the research for Hepatitis C Virus (HCV) and influenza inhibitors to cleave and eliminate targeted proteins by hijacking the powerful cellular degradation systems [64,65]. Conversion of PF74-like scaffolds into PROTACs may promote the identification of a new class of modulators to abrogate normal functions of the HIV-1 CA protein, which, relative to ordinary small molecules, can improve our knowledge of target-based drug design and support novel therapeutic strategies.
Formosanin C induces autophagy-mediated apoptosis in multiple myeloma cells through the PI3K/AKT/mTOR signaling pathway
Published in Hematology, 2022
Ping Chen, Sungui Wu, Xiaoqing Dong, Min Zhou, Peipei Xu, Bing Chen
Autophagy is a lysosome-dependent protein degradation pathway that removes excess protein aggregates and damaged or dysfunctional organelles [17]. Autophagy plays a double-edged role in tumors. It is linked to cell survival/proliferation and is beneficial for tumor maintenance; it can recycle damaged organelles, relieve metabolic stress, overcome nutrient deprivation, and regulate cellular homeostasis [18, 19]. However, excessive autophagy may block tumor survival or result in cell death [20]. In MM, chemotherapeutic drug-induced autophagy play a pro-survival and drug-resistance role by relieving cellular stress caused by toxic stimulation, or a subversive role by triggering autophagic cell death [21]. Therefore, inhibiting MM cell survival/proliferation and promoting MM cell death by regulating autophagy may be novel therapeutic strategy [22].