While cellular proteins were initially thought to be stable, research over the last decades has firmly established that intracellular protein degradation is an active and highly regulated process: Lysosomal, proteasomal, and mitochondrial degradation systems were identified and found to be involved in a staggering number of biological functions. Here, we provide a global overview of the diverse roles of cellular protein degradation using seven categories: homeostasis, regulation, quality control, stoichiometry control, proteome remodeling, immune surveillance, and baseline turnover. Using selected examples, we outline how proteins are degraded and why this is functionally relevant.
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http://dx.doi.org/10.1146/annurev-cellbio-120420-091943 | DOI Listing |
Mol Biol Rep
January 2025
Department of Biology, Adelphi University, One South Avenue, P.O. Box 701, Garden City, NY, 11530-0701, USA.
Background: von Hippel-Lindau (VHL) hereditary cancer syndrome is caused by mutations in the VHL tumor suppressor gene and is characterized by a predisposition to form various types of tumors, including renal cell carcinomas, hemangioblastomas, and pheochromocytomas. The protein products of the VHL gene, pVHL, are part of an ubiquitin ligase complex that tags hypoxia inducible factor alpha (HIF-α) for proteosomal degradation. pVHL has also been reported to bind to atypical protein kinase C (aPKC).
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong SAR 999077, China.
RNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development.
View Article and Find Full Text PDFACS Chem Biol
January 2025
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Conventional small-molecule drugs primarily operate by inhibiting protein function, but this approach is limited when proteins lack well-defined ligand-binding pockets. Targeted protein degradation (TPD) offers an alternative approach by harnessing cellular degradation pathways to eliminate specific proteins. Recent studies have expanded the potential of TPD by identifying additional E3 ligases, with DCAF16 emerging as a promising candidate for facilitating protein degradation through both proteolysis-targeting chimera (PROTAC) and molecular glue mechanisms.
View Article and Find Full Text PDFBiomed Rep
March 2025
Department of Physical Therapy, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto 607-8175, Japan.
In age-related peripheral neurodegeneration, changes in the promotion or inhibition of endoplasmic reticulum (ER) stress response related to the ubiquitin-proteasome degradation system (UPS), autophagy and apoptosis signaling factors during aging remain unclear. In the present study, the expression of ER stress response signaling-related protein factors was examined in tibial nerves during aging in rats. Tibial nerves were extracted from continuously housed rats at 20, 50, 70, 90 and 105 weeks of age.
View Article and Find Full Text PDFFront Bioinform
January 2025
Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, Hunan, China.
The precise role of lncRNAs in skeletal muscle development and atrophy remain elusive. We conducted a bioinformatic analysis of 26 GEO datasets from mouse studies, encompassing embryonic development, postnatal growth, regeneration, cell proliferation, and differentiation, using R and relevant packages (limma et al.).
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