AI Article Synopsis

  • The study explores how gene expression regulates the proteome in cervical cancer cells by monitoring changes in the transcriptome, translatome, proteome, and RNA-protein interactions.
  • It identifies responses to misfolded proteins and oxidative stress, showing that many genes continue to be expressed even during stress, revealing new insights into the unfolded protein response.
  • The findings highlight various regulatory pathways and behaviors of genes under stress, emphasizing the complexity of gene regulation in maintaining cell health.

Article Abstract

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185107PMC
http://dx.doi.org/10.7554/eLife.39054DOI Listing

Publication Analysis

Top Keywords

response proteostatic
8
insights cellular
4
cellular temporal
4
temporal response
4
proteostatic stress
4
stress maintaining
4
maintaining healthy
4
healthy proteome
4
proteome involves
4
involves layers
4

Similar Publications

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 PDF

Molecular and functional characterization of Accl(2)efl: A biomarker for heavy metal stress in Apis cerana cerana.

Ecotoxicol 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 PDF

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 PDF

Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.

Redox 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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!