Search results for "protein processing"
showing 10 items of 144 documents
Post-translational modifications on RNA-binding proteins: accelerators, brakes, or passengers in neurodegeneration?
2021
RNA-binding proteins (RBPs) are critical players in RNA expression and metabolism, thus, the proper regulation of this class of proteins is critical for cellular health. Regulation of RBPs often occurs through post-translational modifications (PTMs), which allow the cell to quickly and efficiently respond to cellular and environmental stimuli. PTMs have recently emerged as important regulators of RBPs implicated in neurodegenerative disorders, in particular amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we summarize how disease-associated PTMs influence the biophysical properties, molecular interactions, subcellular localization, and function of ALS/FTD-linked …
Phenylpropanoid and phenylisoprenoid metabolites from Asteraceae species as inhibitors of protein carbonylation.
2011
Abstract Three phenolic antioxidant and anti-inflammatory compounds: 7-methylaromadendrin, isoprenylhydroquinone glucoside, and 3.5-dicaffeoylquinic acid methyl ester, all isolated from Western Mediterranean Asteraceae species, have been studied for their inhibitory activity against protein carbonylation, a harmful post-translational modification of peptide chains associated with degenerative diseases. All compounds have proven to be effective, with 50% inhibitory concentration (IC 50 ) values in the micromolar range, against bovine serum albumin carbonylation caused by hypochlorite, peroxynitrite, and phorbol ester-induced leukocyte oxidative burst.
Modification of the proteolytic fragmentation pattern upon oxidation of cysteines from ribulose 1,5-bisphosphate carboxylase/oxygenase.
2003
The proteolytic susceptibility of the native CO 2 -fixing photosynthetic enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39, Rubisco) has been shown to increase in vitro after oxidative treatments that affect cysteine thiols. A limited incubation of oxidized (pretreated with the disulfide cystamine) Rubisco from Chlamydomonas reinhardtii with subtilisin or proteinase K generated fragments of molecular mass about 53 kDa (band I in SDS-PAGE) and 47 kDa (band II) derived from the large subunit (55 kDa) of the enzyme. In contrast, proteolysis of the reduced Rubisco (pretreated with the free thiol cysteamine) produced only the 53 kDa band. The same fragmentation pattern was repr…
Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2 receptor in Chinese hamster ovary cells.
1999
Rat bradykinin B2 receptor from unstimulated Chinese hamster ovary cells transfected with the corresponding cDNA has been isolated, and subsequent mass spectrometric analysis of multiple phosphorylated species and of the palmitoylation attachment site is described. Bradykinin B2 receptor was isolated on oligo(dT)-cellulose using N-(epsilon-maleimidocaproyloxy)succinimide-Met-Lys-bradykinin coupled to a protected (dA)30-mer. This allowed a one-step isolation of the receptor on an oligo(dT)-cellulose column via variation solely of salt concentration. After enzymatic in-gel digestion, matrix-assisted laser desorption ionization and electrospray ion trap mass spectrometric analysis of the isola…
Sequence evolution, processing, and posttranslational modification of zonadhesin D domains in primates, as inferred from cDNA data
2005
Zonadhesin is a mammalian transmembrane sperm ligand. Precursor zonadhesin essentially consists of MAM (meprin/A5 antigen/mu receptor tyrosine phosphatase) domains, a mucin-like repeat, and D domains (homologous to von Willebrand D). Recent immunovisualization and binding assays indicate that zonadhesin D domains 1–3 bind postacrosomally to the zona pellucida. This feature has attracted considerable interest in the evolution of zonadhesin and its possible biological and biomedical implications. Previous molecular evolutionary analyses, however, were confined to cDNA sequences of only few distantly related species. Moreover, except for rabbit and pig, little is known about zonadhesin’s proce…
Influence of ADAM10 on prion protein processing and scrapie infectiosity in vivo.
2009
Abstract Both the cellular prion protein (PrPc) and the amyloid precursor protein (APP) are physiologically subjected to complex proteolytic processing events. While for APP the proteinases involved – alpha-, beta- and gamma-secretase – have been identified in vitro and in vivo, the cleavage of PrPc by now has been linked only to the shedding activity of the metalloproteinase ADAM10 and/or ADAM17 in cell culture. Here we show that neuronal overexpression of the alpha-secretase ADAM10 in mice reduces all PrPc species detected in the brain instead of leading to enhanced amounts of specific cleavage products of PrPc. Additionally, the incubation time of mice after scrapie infection is signific…
The N-glycan processing in HT-29 cells is a function of their state of enterocytic differentiation. Evidence for an atypical traffic associated with …
1991
International audience; When the human colon cancer cells HT-29 undergo enterocytic differentiation, they correctly process their N-glycans, whereas their undifferentiated counterpart are unable to process Man9-8-GlcNAc2 species, the natural substrate of alpha-mannosidase I. As this enzyme is fully active in both HT-29 cell populations, we hypothesize that N-glycoproteins are unable to reach the cis Golgi, the site where alpha-mannosidase I has been localized. We have demonstrated this point by using 1-deoxymannojirimycin, leupeptin, and monensin. In the presence of 1-deoxymannojirimycin, a specific inhibitor of alpha-mannosidase I, differentiated HT-29 cells, as expected, accumulate Man9-8…
Heat shock proteins in hematopoietic malignancies
2012
Inducible heat shock proteins are molecular chaperones whose expression is increased after many different types of stress. They have a protective function helping the cell to cope with lethal conditions. Their basal expression is low in nonstressed, normal and nontransformed cells. However, in cancer cells and particularly in hematological malignancies, they are surprisingly abundant. Malignant cells have to rewire their metabolic requirements and therefore have a higher need for chaperones. This cancer cell addiction for HSPs is the basis for the use of HSP inhibitors in cancer therapy. HSPs have been shown to interact with different key apoptotic proteins. As a result, HSPs can essentiall…
Chaperone action in the posttranslational topological reorientation of the hepatitis B virus large envelope protein: Implications for translocational…
2003
The large L envelope protein of the hepatitis B virus utilizes a new folding pathway to acquire a dual transmembrane topology in the endoplasmic reticulum (ER). The process involves cotranslational membrane integration and subsequent posttranslational translocation of its preS subdomain into the ER. Here, we demonstrate that the conformational and functional heterogeneity of L depends on the action of molecular chaperones. Using coimmunoprecipitation, we observed specific interactions between L and the cytosolic Hsc70, in conjunction with Hsp40, and between L and the ER-resident BiP in mammalian cells. Complex formation between L and Hsc70 was abolished when preS translocation was artifici…
Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation
1995
Processing of the hepatitis C virus polyprotein is mediated by host cell signalases and at least two virally encoded proteinases. Of these, the serine-type proteinase encompassing the amino-terminal one-third of NS3 is responsible for cleavage at the four sites carboxy terminal of NS3. The activity of this proteinase is modulated by NS4A, a 54-amino-acid polyprotein cleavage product essential for processing at the NS3/4A, NS4A/4B, and NS4B/5A sites and enhancing cleavage efficiency between NS5A and NS5B. Using the vaccinia virus-T7 hybrid system to express hepatitis C virus polypeptides in BHK-21 cells, we studied the role of NS4A in proteinase activation. We found that the NS3 proteinase a…