Huntington disease (HD) is a neurodegenerative disorder caused by an elongated polyglutamine tract in huntingtin (htt). htt normally undergoes different posttranslational modifications (PTMs), including phosphorylation, SUMOylation, ubiquitination, acetylation, proteolytic cleavage, and palmitoylation. In the presence of the HD mutation, some PTMs are significantly altered and can result in changes in the clinical phenotype. A rate-limiting PTM is defined as one that can result in significant effects on the phenotype in animal models. For example, the prevention of proteolysis at D586 as well as constitutive phosphorylation at S13 and S16 can obviate the expression of phenotypic features of HD. The enzymes involved in these modifications such as caspase-6, the IκB kinase (IKK) complex, and still to be characterized phosphatases therefore represent promising therapeutic targets for HD. Identifying and testing specific modulators of PTMs now constitute the next big challenges in order to further validate these targets and proceed towards the goal of a mechanism-based treatment for HD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200085 | PMC |
| http://dx.doi.org/10.1177/1073858410390378 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mapping O- and N-Glycosylation in Transmembrane and Interface Regions of Proteins: Insights from a Database Search Study.
Int J Mol Sci
January 2025
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independenței Str., 050095 Bucharest, Romania.
Glycosylation is a critical post-translational modification that influences protein folding, stability and function. While extensively studied in extracellular and intracellular regions, glycosylation within transmembrane (TM) regions and at membrane interfaces remains poorly understood. This study aimed to map O- and N-glycosylation sites in these regions using a comprehensive database search and structural validation where possible.
View Article and Find Full Text PDFS6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.
Int J Mol Sci
December 2024
Division of Cancer, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer.
View Article and Find Full Text PDFThe Role of Vimentin Peptide Citrullination in the Structure and Dynamics of HLA-DRB1 Rheumatoid Arthritis Risk-Associated Alleles.
Int J Mol Sci
December 2024
Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Citrullination, a post-translational modification (PTM), plays a critical role in rheumatoid arthritis (RA) by triggering immune responses to citrullinated self-antigens. Some HLA-DRB1 genes encode molecules with the shared epitope (QKRAA/QRRAA) sequence in the peptide-binding groove which preferentially presents citrulline-modified peptides, like vimentin, that intensifies the immune response in RA. In this study, we used computational approaches to evaluate intermolecular interactions between vimentin peptide-ligands (with/without PTM) and HLA-DRB1 alleles associated with a significantly increased risk for RA development.
View Article and Find Full Text PDFRegulation of Histone Acetylation Modification on Biosynthesis of Secondary Metabolites in Fungi.
Int J Mol Sci
December 2024
Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
The histone acetylation modification is a conservative post-translational epigenetic regulation in fungi. It includes acetylation and deacetylation at the lysine residues of histone, which are catalyzed by histone acetyltransferase (HAT) and deacetylase (HDAC), respectively. The histone acetylation modification plays crucial roles in fungal growth and development, environmental stress response, secondary metabolite (SM) biosynthesis, and pathogenicity.
View Article and Find Full Text PDFPRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of .
Molecules
December 2024
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico.
Protein arginine methyltransferase 5 (PRMT5) is an enzyme that produces monomethyl arginine (MMA) and symmetric dimethyl arginine (sDMA), post-translational modifications that regulate several cellular processes, including stage conversion in parasitic protozoans. , the etiologic agent of human amebiasis, has two stages in its life cycle, the trophozoite, which is the replicative form, and the cyst, corresponding to the infective phase. The study of the molecular mechanisms that regulate differentiation in this parasite has been overdue because of a lack of efficient protocols for in vitro encystment.
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!