A molecular switch for Cdc48 activity and localization during oxidative stress and aging
Reichmann, D.; Radzinski, M.; Yogev, O.; Yesharim, Y.; Brielle, E. S.; Israeli, R.; Fassler, R.; Melamed-Book, N.; Shai, N.; Arkin, I. T.; Pick, E.; Ravid, T.; Schuldiner, M.
Show abstract
Control over a healthy proteome begins with the birth of the polypeptide chain and ends with coordinated protein degradation. One of the major players in eukaryotic protein degradation is the essential and highly conserved ATPase, Cdc48 (p97/VCP in mammals). Cdc48 mediates clearance of misfolded proteins from the nucleus, cytosol, ER, mitochondria, and more. Here we dissect the crosstalk between cellular oxidation and Cdc48 activity by identification of a redox-sensitive site, Cys115. By integrating proteomics, biochemistry, microscopy, and bioinformatics, we show that removal of Cys115s redox-sensitive thiol group leads to accumulation of Cdc48 in the nucleus and consequently, results in severe defects in the oxidative stress response, mitochondrial fragmentation, and a decrease in ERAD and sterol biogenesis. We have thus identified a unique redox switch in Cdc48, which may provide a clearer picture of the importance of Cdc48s localization in maintaining a \"healthy\" proteome during oxidative stress and chronological aging in yeast.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Mitochondrial protein heterogeneity stems from the stochastic nature of co-translational protein targeting in cell senescence 94%
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains 94%
- Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption 94%
Similar papers in this journal
- Overexpression of Ssd1 and calorie restriction extend yeast replicative lifespan by preventing deleterious age-dependent iron uptake 96%
- Metabolic stress is a primary pathogenic event in transgenic Caenorhabditis elegans expressing neuronal human amyloid-β 95%
- The Neuron-specific IIS/FOXO Transcriptome in Aged Animals Reveals Regulatory Mechanisms of Neuronal and Cognitive Aging 95%
Similar papers in this journal
Similar papers in this journal
- Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans 94%
- Deep Proteome Profiling of Human Mammary Epithelia at Lineage and Age Resolution 93%
- Heparan sulfate modified proteins affect cellular processes central to neurodegeneration and modulate presenilin function 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.