Deciphering the inositol-requiring enzyme 1 (IRE1) signaling pathway is fundamentally important for understanding the unfolded protein response (UPR). The ubiquitination of proteins residing on the endoplasmic reticulum (ER) membrane has been reported to be involved in the UPR, although the mechanism has yet to be fully elucidated. Using immunoprecipitation and mass spectrometry, IRE1 was identified as a substrate of the E3 ligase CHIP (carboxyl terminus of HSC70-interacting protein) in HEK293 cells under geldanamycin-induced ER stress. Two residues of IRE1, Lys(545) and Lys(828), were targeted for Lys(63)-linked ubiquitination. Moreover, in CHIP knockdown cells, IRE1 phosphorylation and the IRE1-TRAF2 interaction were nearly abolished under ER stress, which may be due to lacking ubiquitination of IRE1 on Lys(545) and Lys(828), respectively. The cellular responses were evaluated, and the data indicated that CHIP-regulated IRE1/TRAF2/JNK signaling antagonized the senescence process. Therefore, our findings suggest that CHIP-mediated ubiquitination of IRE1 contributes to the dynamic regulation of the UPR.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215236 | PMC |
| http://dx.doi.org/10.1074/jbc.M114.562868 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Advanced PROTAC and Quantitative Proteomics Strategy Reveals Bax Inhibitor-1 as a Critical Target of Icaritin in Burkitt Lymphoma.
Int J Mol Sci
December 2024
School of Medicine, Huaqiao University, Quanzhou 362021, China.
Understanding the molecular targets of natural products is crucial for elucidating their mechanisms of action, mitigating toxicity, and uncovering potential therapeutic pathways. Icaritin (ICT), a bioactive flavonoid, demonstrates significant anti-tumor activity but lacks defined molecular targets. This study employs an advanced strategy integrating proteolysis targeting chimera (PROTAC) technology with quantitative proteomics to identify ICT's key targets.
View Article and Find Full Text PDFTrehalose Ameliorates Nonalcoholic Fatty Liver Disease by Regulating IRE1α-TFEB Signaling Pathway.
J Agric Food Chem
December 2024
Department of Clinical Nutrition and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic lipid deposition, is one of the most prevalent chronic metabolic disorders globally, and its pharmaceutical treatments are still limited. Excessive lipid accumulation triggers endoplasmic reticulum (ER) stress and autophagy flux dysfunction, which are important mechanisms for NAFLD. Trehalose (Tre), a natural disaccharide, has been identified to reduce hepatic steatosis and glucose intolerance.
View Article and Find Full Text PDFDynamic modulation of IRE1α-XBP1 signaling by adenovirus.
bioRxiv
December 2024
Department of Radiation Oncology and Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland USA.
The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates in the expression of downstream genes that collectively restore protein homeostasis. The model pathogen adenovirus serotype 5 (HAdV5) activates the UPR via the signaling axis formed by inositol-requiring enzyme type 1 (IRE1α) and the X-box binding protein 1 (XBP1), a transcription factor required for immune function.
View Article and Find Full Text PDFEffect of 2,5-hexanedione on rat ovarian granulosa cell apoptosis involves endoplasmic reticulum stress-dependent m-TOR signaling pathway.
J Toxicol Environ Health A
December 2024
Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations & School of Public Health, Changsha Medical University, Changsha, China.
Occupational exposure to N-hexane/2,5-hexanedione (2,5-HD) was found to adversely affect reproductive functions in females. However, there are few studies regarding the mechanisms underlying reproductive system damage initiated by 2,5-HD. Several studies demonstrated that 2,5-HD exerts hormonal dysfunctions in females by promoting apoptosis using rat ovarian granulosa cells (GCs) as a model.
View Article and Find Full Text PDFSingle-nucleus transcriptomic analysis reveals the regulatory circuitry of myofiber XBP1 during regenerative myogenesis.
iScience
December 2024
Institute of Muscle Biology and Cachexia, University of Houston College of Pharmacy, Houston, TX 77204, USA.
Article Synopsis
- The unfolded protein response (UPR) in skeletal muscle is activated during stress, but its role in muscle regeneration is not well understood.
- In a study, researchers found that the gene XBP1, crucial for the UPR, is vital for muscle regeneration, as its absence hinders recovery in adult mice.
- Analysis revealed that XBP1 affects both muscle cell function and the behavior of surrounding non-muscle cells, indicating that it plays a key role in muscle repair through multiple mechanisms.
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!