Protein folding and clearance networks sense and respond to misfolded and aggregation-prone proteins by activating cytoprotective cell stress responses that safeguard the proteome against damage, maintain the health of the cell, and enhance lifespan. Surprisingly, cellular proteostasis undergoes a sudden and widespread failure early in Caenorhabditis elegans adulthood, with marked consequences on proteostasis functions later in life. These changes in the regulation of quality control systems, such as chaperones, the ubiquitin proteasome system and cellular stress responses, are controlled cell-nonautonomously by the proliferation of germline stem cells. Here, we review recent studies examining changes in proteostasis upon transition to adulthood and how proteostasis is modulated by reproduction onset, focusing on C. elegans. Based on these and our own findings, we propose that the regulation of quality control systems is actively remodeled at the point of transition between development and adulthood to influence the subsequent course of aging.
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http://dx.doi.org/10.2174/1389202915666140221005023 | DOI Listing |
bioRxiv
January 2025
Ben-May Institute for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
Insulin degrading enzyme (IDE) is a dimeric 110 kDa M16A zinc metalloprotease that degrades amyloidogenic peptides diverse in shape and sequence, including insulin, amylin, and amyloid-β, to prevent toxic amyloid fibril formation. IDE has a hollow catalytic chamber formed by four homologous subdomains organized into two ~55 kDa N- and C- domains (IDE-N and IDE-C, respectively), in which peptides bind, unfold, and are repositioned for proteolysis. IDE is known to transition between a closed state, poised for catalysis, and an open state, able to release cleavage products and bind new substrate.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Max Planck Institute for Multidisciplinary Sciences, Research Group 'Ubiquitin Signaling Specificity', Am Fassberg 11, Göttingen, Germany.
Mol Cell
December 2024
MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. Electronic address:
Proc Natl Acad Sci U S A
October 2024
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
UBR5 E3 ligase has been associated with cancer susceptibility and neuronal integrity, with functions in chromatin regulation and proteostasis. However, the functions of within animals remain unclear due to lethality in both mammals and flies when disrupted. Using , we show that UBR-5 E3 ligase is required for timely exit of stem fate and complete transition into multiple cell type descendants in an ectodermal blast lineage.
View Article and Find Full Text PDFMolecules
September 2024
Biochemistry & Proteomics Laboratories, Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY 13699-5810, USA.
Proteins are the most common types of biomarkers used in breast cancer (BC) theranostics and management. By definition, a biomarker must be a relevant, objective, stable, and quantifiable biomolecule or other parameter, but proteins are known to exhibit the most variate and profound structural and functional variation. Thus, the proteome is highly dynamic and permanently reshaped and readapted, according to changing microenvironments, to maintain the local cell and tissue homeostasis.
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