Search results for " Post-Translational"
showing 10 items of 148 documents
A multifunctional bicupin serves as precursor for a chromosomal protein of Pisum sativum seeds.
2005
The fact that the psp54 gene codes for p16, a seed chromatin protein of Pisum sativum, has been described previously. In the present paper it is shown that p54, the p16 precursor, also exists as a free polypeptide in pea and that it also yields p38, a second polypeptide from the N-terminal region of p54, which is co-localized at a subcellular level with p16. By using antibodies against pea p16 and p38, it was found that these proteins are present in the members of the tribe Viciae examined. Sequence analysis and 3D modelling indicates that p54 proteins belong to the cupin superfamily, and that they are related to sucrose binding proteins and, to a lesser extent, to vicilin-type seed storage…
News from an Ancient World: Two Novel Astacin Metalloproteases from the Horseshoe Crab
2008
In this work, we report the cloning, heterologous expression, and characterization of two novel astacin proteases from the chelicerate Limulus polyphemus (horseshoe crab), designated as LAST (Limulus astacin) and LAST_MAM (Limulus astacin containing a MAM domain), respectively. The expression pattern showed ubiquitous occurrence of LAST_MAM, while LAST was predominantly restricted to the eyes and brain, indicating a function in the nervous system. Both enzymes contain the characteristic metzincin-type zinc-binding region and Met turn. While LAST is made up only of the typical prodomain and astacin-like protease domain, LAST_MAM contains an additional MAM (meprin A5 protein tyrosine phosphat…
Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition
2020
Abstract The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. In this study, transcriptional profiling after pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being the most pronounced. Combining menin-MLL inhibition with specific small-molecule kinase inhibitors…
Selective mono-de-O-acetylation of the per-O-acetylated brasilicardin carbohydrate side chain
2021
Abstract Methanol dried over powdered 4 A molecular sieves can be used for a selective mono-de-O-acetylation of the phenolic acetyl group of the per-O-acetyl protected brasilicardin A carbohydrate side chain. This reaction opens a practical procedure for a synthetic access to derivates of the immunosuppressive and cytotoxic natural product brasilicardin A.
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…