We now have a comprehensive inventory of ubiquitin system components. Understanding of any system also needs an appreciation of how components are organised together. Quantitative proteomics has provided us with a census of their relative populations in several model cell types. Here, by examining large scale unbiased data sets, we seek to identify and map those components, which principally reside on the major organelles of the endomembrane system. We present the consensus distribution of > 50 ubiquitin modifying enzymes, E2s, E3s and DUBs, that possess transmembrane domains. This analysis reveals that the ER and endosomal compartments have a diverse cast of resident E3s, whilst the Golgi and mitochondria operate with a more restricted palette. We describe key functions of ubiquitylation that are specific to each compartment and relate this to their signature complement of ubiquitin modifying components.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.semcdb.2021.11.016 | DOI Listing |
J Proteome Res
January 2025
Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon 34134, Republic of Korea.
The E3 ubiquitin ligase neural precursor cell-expressed developmentally down-regulated 4 (NEDD4) is involved in various cancer signaling pathways, including PTEN/AKT. However, its role in promoting gastric cancer (GC) progression is unclear. This study was conducted to elucidate the role of NEDD4 in GC progression.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemical and Systems Biology, Stanford Cancer Institute, School of Medicine Stanford University, Stanford, California 94305-6104, United States.
Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small molecules or biologics to direct proteins to the cellular machinery for destruction. Among the >600 human E3 ligases, CRBN and VHL have served as workhorses for ubiquitin-proteasome system-dependent TPD. Identification of additional E3 ligases capable of supporting TPD would unlock the full potential of this mechanism for both research and pharmaceutical applications.
View Article and Find Full Text PDFBiol Aujourdhui
January 2025
Université de Caen Normandie, CERMN UR4258, Boulevard Becquerel, 14000 Caen, France.
The disruption of proteostasis provides a favourable context for the emergence of therapeutic innovations, in particular by exploiting technologies such as the PROTAC (Proteolysis Targeting Chimera) approach. These technologies aim to selectively target proteins involved in various diseases, including cancer and neurodegenerative diseases, by inducing their specific degradation via the ubiquitin-proteasome system. The PROTAC approach opens new opportunities for restoring altered protein homeostasis and modulating the pathological consequences of proteostasis deregulation.
View Article and Find Full Text PDFbioRxiv
January 2025
Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine, University of Iowa.
Background: Radiation therapy (RT) treats primary and metastatic brain tumors, with about one million Americans surviving beyond six months post-treatment. However, up to 90% of survivors experience RT-induced cognitive impairment. Emerging evidence links cognitive decline to RT-induced endothelial dysfunction in brain microvessels, yet studies of endothelial injury remain limited.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!