Neuroblastoma (NB) stands as a common and formidable malignant tumor among children, characterized by marked tumor heterogeneity and resistance to conventional treatments. Central to the regulation of protein stability, localization, and function is the process of ubiquitination-a critical protein modification. The therapeutic potential of drugs that target deubiquitination, demonstrated in the treatment of refractory multiple myeloma, warrants investigation in the context of NB. This review endeavors to demystify the intricate biological implications of ubiquitination within NB pathology, synthesize the current landscape of preclinical studies focused on the inhibition of the ubiquitin-proteasome system in NB, and assess the viability of this strategy as an innovative therapeutic frontier.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464458 | PMC |
| http://dx.doi.org/10.3389/fonc.2024.1443256 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Locating Polyubiquitin Receptors on the 19S Regulatory Proteasome of by Cross-Linking Mass Spectrometry.
J Am Soc Mass Spectrom
January 2025
Department of Molecular Biosciences, University of Texas, Austin, Texas 78712, United States.
The effectiveness of state-of-the-art cross-linking strategies and mass spectrometry (MS) detection was explored in an important biological context, namely, the ubiquitin-proteasome system, which is responsible for most of the regulated protein degradation in eukaryotic cells. The locations of possible binding sites on the 19S proteasome regulatory particle for Lys linked polyubiquitin chains were examined using cross-linking strategies and MS based detection by comparing two types of cross-linkers: a (bis)-sulfosuccinimidyl suberate (BS) and diethyl suberothioimidate (DEST). The well-established BS-based strategy produced 328 cross-linked peptides; however, no ubiquitin-19S cross-links were observed.
View Article and Find Full Text PDFHarnessing the ubiquitin proteasome system as a key player in stem cell biology.
Biofactors
January 2025
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Intracellular proteins take part in almost every body function; thus, protein homeostasis is of utmost importance. The ubiquitin proteasome system (UPS) has a fundamental role in protein homeostasis. Its main role is to selectively eradicate impaired or misfolded proteins, thus halting any damage that could arise from the accumulation of these malfunctioning proteins.
View Article and Find Full Text PDFProstate cancer-selective anticancer action of an oxindole derivative via HO-1-mediated disruption of metabolic reprogramming.
Chem Biol Interact
January 2025
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address:
Prostate cancer, the second leading cause of cancer-related mortality in men, exhibits distinct metabolic reprogramming involving zinc and citrate metabolism. This study investigated whether targeting this unique metabolic profile could offer an effective therapeutic approach. A series of novel oxindole derivatives were synthesized and evaluated for their inhibitory effects on transcription factors (TFs) and antiproliferative activity across various cancer cell lines.
View Article and Find Full Text PDFThe deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.
Sci Adv
January 2025
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.
View Article and Find Full Text PDFA patent review of von Hippel-Lindau (vhl)-recruiting chemical matter: E3 ligase ligands for PROTACs and targeted protein degradation (2019-present).
Expert Opin Ther Pat
January 2025
Centre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee, UK.
Introduction: The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL has become an attractive target for proteolysis targeting chimeras (PROTACs), bifunctional molecules that can induce degradation of neo-substrate proteins. The development of VHL inhibitors and PROTACs has seen rapid development since disclosure of the first non-peptidic VHL ligand (2012).
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!