Search results for "Protein Processing"
showing 10 items of 144 documents
Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription.
2008
A sequence of amyloid precursor protein (APP) cleavages culminates in the sequential release of the APP intracellular domain (AICD) and the amyloid beta peptide (Abeta) and/or p3 fragment. One of the environmental factors favouring the accumulation of AICD appears to be a rise in intracellular pH. Here we further identified the metabolism and subcellular localization of artificially expressed constructs under such conditions. We also co-examined the mechanistic lead up to the AICD accumulation and explored possible significances for its increased expression. We found that most of the AICD generated under pH neutralized conditions is likely cleaved from C83. While the AICD surplus was unable…
Protease-mediated processing of Argonaute proteins controls small RNA association
2020
SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a cha…
Tributyltin(Iv) butyrate: A novel epigenetic modifier with er stress-and apoptosis-inducing properties in colon cancer cells
2021
Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (1H, 13C and 119Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric enviro…
NMR structure of a non-conjugatable, ADP-ribosylation associated, ubiquitin-like domain from Tetrahymena thermophila polyubiquitin locus.
2019
Abstract Background Ubiquitin-like domains (UbLs), in addition to being post-translationally conjugated to the target through the E1-E2-E3 enzymatic cascade, can be translated as a part of the protein they ought to regulate. As integral UbLs coexist with the rest of the protein, their structural properties can differ from canonical ubiquitin, depending on the protein context and how they interact with it. In this work, we investigate T.th-ubl5, a UbL present in a polyubiquitin locus of Tetrahymena thermophila, which is integral to an ADP-ribosyl transferase protein. Only one other co-occurrence of these two domains within the same protein has been reported. Methods NMR, multiple sequence al…
Regulation of NOS expression in vascular diseases
2020
Nitric oxide synthases (NOS) are the major sources of nitric oxide (NO), a small bioactive molecule involved in the regulation of many cellular processes. One of the most prominent functions of NO is regulation of vasodilatation and thereby control of blood pressure. Most important for vascular tone is NOS3. Endothelial NOS3-generated NO diffuses into the vascular smooth muscle cells, activates the soluble guanylate cyclase resulting in enhanced cGMP concentrations and smooth muscle cell relaxation. However, more and more evidence exist that also NOS1 and NOS2 contribute to vascular function. We summarize the current knowledge about the regulation of NOS expression in the vasculature by tra…
Membrane topology and post-translational modification of the Saccharomyces cerevisiae essential protein Rot1.
2007
ROT1 is an essential gene that has been related to cell wall biosynthesis, the actin cytoskeleton and protein folding. In order to help to understand its molecular function, we carried out a characterization of the Rot1 protein. It is primarily located at the endoplasmic reticulum-nuclear membrane facing the lumen. Rot1 migrates more slowly than expected, which might suggest post-translational modification. Our results indicate that Rot1 is a protein that is neither GPI-anchored nor O-glycosylated. In contrast, it is N-glycosylated. By a directed mutagenesis of several Asn residues, we identified that the protein is simultaneously glycosylated at N103, N107 and N139. Although the mutation o…
Procollagen C-proteinase Enhancer Stimulates Procollagen Processing by Binding to the C-propeptide Region Only*
2011
Background: Procollagen C-proteinase enhancer-1 (PCPE-1) is an extracellular glycoprotein that increases activity of certain zinc metalloproteinases involved in tissue development and repair. Results: PCPE-1 binds uniquely to the C-propeptide region of the procollagen molecule. Conclusion: PCPE-1 enhances proteolysis by binding solely to the procollagen C-propeptides. Significance: These data may lead to future applications in the development of antifibrotic therapies.
Posttranslational processing of human alpha 2-HS glycoprotein (human fetuin). Evidence for the production of a phosphorylated single-chain form by he…
1994
alpha 2-HS glycoprotein (alpha 2-HS) is a major protein occurring in human blood and calciferous tissues. Due to extensive sequence identity, alpha 2-HS has been grouped with the fetuins, a family of proteins that occur in fetal plasma in high concentrations. Native alpha 2-HS undergoes a series of posttranslational modifications including proteolytic processing, multiple N-glycosylations and O-glycosylations, and sulfation of the carbohydrate side chains. Various two-chain forms of alpha 2-HS have been prepared from human plasma, however, the single-chain precursor has not yet been isolated. Here, we have studied the biosynthesis of alpha 2-HS by a human hepatoma cell line, HepG2. We demon…
C-Glycosyl amino acids through hydroboration-cross-coupling of exo-glycals and their application in automated solid-phase synthesis.
2013
O-Glycosylation is one of the most important post-translational modifications of proteins. The attachment of carbohydrates to the peptide backbone influences the conformation as well as the solubility of the conjugates and can even be essential for binding to specific ligands in cell-cell interactions or for active transport over membranes. This makes glycopeptides an interesting class of compounds for medical applications. To enhance the long-term availability of these molecules in vivo, the stabilization of the glycosidic bond between the amino acid residue and the carbohydrate is of interest. The described modular approach affords β-linked C-glycosyl amino acids by a sequence of Petasis …
Human Enterovirus Group B Viruses Rely on Vimentin Dynamics for Efficient Processing of Viral Nonstructural Proteins.
2019
A virus needs the host cell in order to replicate and produce new progeny viruses. For this, the virus takes over the host cell and modifies it to become a factory for viral proteins. Irrespective of the specific virus family, these proteins can be divided into structural and nonstructural proteins. Structural proteins are the building blocks for the new progeny virions, whereas the nonstructural proteins orchestrate the takeover of the host cell and its functions. Here, we have shown a mechanism that viruses exploit in order to regulate the host cell. We show that viral protein synthesis induces vimentin cages, which promote production of specific viral proteins that eventually control apo…