Sphingomyelin synthase 1 (SMS1) is an essential enzyme that catalyses the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide in eukaryotic cells. We previously studied the structure of the human SMS1 gene in detail, and identified its numerous transcripts. We revealed mRNA isoforms that varied in the 5'-untranslated region (UTR) and encoded the full-length protein as well as transcripts resulting from alternative combinations of the exons in the gene's coding region and the 3'-UTR. In the present work, we used real-time PCR data to determine the expression patterns of SMS1 transcripts encoding the full-length protein and the alternative transcripts whose coding region had been interrupted by their alternative exons, which are the conserved portions of intron VII. Our results indicate that the amount of SMS1 transcripts varies considerably between different human tissues. The mechanisms controlling the level of SMS1 transcripts might include tissue-specific intron polyadenylation causing the appearance of truncated transcripts not involved in the synthesis of the full-length protein SMS1.
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http://dx.doi.org/10.1007/s11033-013-2783-0 | DOI Listing |
J Biol Chem
January 2025
Department of Bioengineering, School of Engineering, The University of Tokyo; Institute of Medical Science, The University of Tokyo; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo; Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, Japan. Electronic address:
Post-translational modification of proteins is a crucial biological reaction that regulates protein functions by altering molecular properties. The specific detection of such modifications in proteins has made significant contributions to molecular biology research and holds potential for future drug development applications. In HIV research, for example, tyrosine sulfation at the N-terminus of C-C chemokine receptor type 5 (CCR5) is considered to significantly enhance HIV infection efficiency.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Electronic address:
Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Lipopolysaccharides (LPS) are bacterial mediators of neuroinflammation that have been detected in close association with pathological protein aggregations of Alzheimer's disease. LPS induce the release of cytokines by microglia and mediate the upregulation of inducible nitric oxide synthase (iNOS)-a mechanism also associated with amyloidosis. Curcumin is a recognized natural medicine but has extremely low bioavailability.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by an array of mutations in the dystrophin gene, with the most commonly mutated regions being exons 48-55. One of the several existing approaches to treat DMD is gene therapy, based on alternative splicing and mutant exon skipping. Testing of such therapy requires animal models that carry mutations homologous to those found in human patients.
View Article and Find Full Text PDFMolecules
December 2024
Resolute Bio, 48 Dunham Rd., Suite 5400, Beverly, MA 01915, USA.
A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides.
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