Maintaining a healthy proteome involves all layers of gene expression regulation. By quantifying temporal changes of the transcriptome, translatome, proteome, and RNA-protein interactome in cervical cancer cells, we systematically characterize the molecular landscape in response to proteostatic challenges. We identify shared and specific responses to misfolded proteins and to oxidative stress, two conditions that are tightly linked. We reveal new aspects of the unfolded protein response, including many genes that escape global translation shutdown. A subset of these genes supports rerouting of energy production in the mitochondria. We also find that many genes change at multiple levels, in either the same or opposing directions, and at different time points. We highlight a variety of putative regulatory pathways, including the stress-dependent alternative splicing of aminoacyl-tRNA synthetases, and protein-RNA binding within the 3' untranslated region of molecular chaperones. These results illustrate the potential of this information-rich resource.
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http://dx.doi.org/10.7554/eLife.39054 | DOI Listing |
Autophagy
January 2025
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Postmitotic skeletal muscle critically depends on tightly regulated protein degradation to maintain proteomic stability. Impaired macroautophagy/autophagy-lysosomal or ubiquitin-proteasomal protein degradation causes the accumulation of damaged proteins, ultimately accelerating muscle dysfunction with age. While studies have demonstrated the complementary nature of these systems, their interplay at the organism levels remains poorly understood.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University, Jining Medical University, Jining, Shandong Province, China. Electronic address:
The expanded lethal (2) essential for life [l(2)efl] gene family is responsive to proteostatic stresses. Their protein products are core components of the stress response mechanism and are emerging as promising biomarkers for cellular stress in Apis mellifera. However, l(2)efl (LOC410857) uniquely remains unresponsive to heat stress within this gene family, and research examining its role in adaptation to other types of stress across diverse bee species is scarce.
View Article and Find Full Text PDFFEBS J
December 2024
Department of Anatomy and Cell Biology, The University of Western Ontario, London, Canada.
Co-chaperones are key elements of cellular protein quality control. They cooperate with the major heat shock proteins Hsp70 and Hsp90 in folding proteins and preventing the toxic accumulation of misfolded proteins upon exposure to stress. Hsp90 interacts with the co-chaperone stress-inducible phosphoprotein 1 (Sti1/Stip1/Hop) and activator of Hsp90 ATPase protein 1 (Aha1) among many others.
View Article and Find Full Text PDFRedox Biol
February 2025
Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK; Department of Pharmacology and Molecular Sciences and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE).
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720, USA.
The Unfolded Protein Response (UPR) was discovered in budding yeast as a mechanism that allows cells to adapt to ER stress. While the Ire1 branch of this pathway is highly conserved, it is not thought to be important for cellular homeostasis in the absence of stress. Surprisingly, we found that removal of UPR activity led to pervasive aneuploidy in budding yeast cells, suggesting selective pressure resulting from UPR-deficiency.
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