AI Article Synopsis
Article Abstract
In the nervous system, proteasomes are important for proteolysis and cellular homeostasis of neurons and glial cells and for brain health. Proteasome function declines with age in many tissues, including the nervous system, and this decline affects many of the nervous system processes important to brain health and may be related to age-related cognitive decline. Therefore, we analyzed the factors that contribute to this decline in function using the brain of mice from different months of life. Peptidase activity of proteasomes in crude extracts decreased with aging, while ubiquitinated proteins increased with aging. Additionally, there was a tendency for the number of subunits that form proteasomes to decrease slightly with age. On the other hand, ump1, which is required for proteasome formation, accumulated with age. Therefore, analysis of proteasome dynamics in each month revealed that proteasome formation decreased with aging. This study suggests that with aging, not only 20S proteasome function but also 26 proteasome function decreases, the decline in proteasome function is due to the lack of proteasome formation, the PA28-20S-PA700 complex, which is involved in immunity, increases in the brain, and one factor in this lack of proteasome formation is that the proteins called UMP1.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/gtc.13113 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Quantitative DIA-based proteomics unveils ribosomal biogenesis pathways associated with increased final size in three-year-old Chinese mitten crab (Eriocheir sinensis).
BMC Genomics
January 2025
Key Laboratory of Ecological Protection and Restoration of Typical Plateau Wetlands, Bijie, Guizhou Province, 551700, China.
Background: Temperature is a key determinant of ectotherms distribution and growth. During the Eriocheir sinensis breeding process, it was observed that crabs in high latitudes and altitude areas with low temperatures undergo diapause, they would overwinter and continue to grow into three-year-old individuals, whose final body size is significantly larger than the normal two-year-old crabs. The hepatopancreas is responsible for maintaining the nutritional balance and energy required for the crab survival.
View Article and Find Full Text PDFERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.
Nat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
View Article and Find Full Text PDFSynthesis and functional screening of novel inhibitors targeting the HDAC6 zinc finger ubiquitin-binding domain.
Eur J Med Chem
December 2024
SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address:
Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.
View Article and Find Full Text PDFInducers of Autophagy and Cell Death: Focus on Copper Metabolism.
Ecotoxicol Environ Saf
January 2025
State Key Laboratory of Swine and Poultry Breeding Industry, Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chendu 611130, PR China. Electronic address:
Copper is an essential trace element in biological systems, playing a key role in various physiological functions, including redox reactions and energy metabolism. However, an imbalance in copper homeostasis can induce oxidative stress, mitochondrial dysfunction, and inhibition of the ubiquitin-proteasome system, ultimately leading to significant cytotoxicity and cell death. According to recent research, copper can bind to lipoylation sites on proteins involved in the tricarboxylic acid cycle, causing aggregation of lipoylated proteins, the loss of Fe-S cluster proteins, proteotoxic stress, and ultimately, cell death.
View Article and Find Full Text PDFSquamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.
Adv Sci (Weinh)
January 2025
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.
View Article and Find Full Text PDFWant 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!