Ubiquitous Protein (ubiquitous + protein)

Distribution by Scientific Domains


Selected Abstracts


Nuclear factor TDP-43 can affect selected microRNA levels

FEBS JOURNAL, Issue 10 2010
Emanuele Buratti
TDP-43 has recently been described as the major component of the inclusions found in the brain of patients with a variety of neurodegenerative diseases, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 is a ubiquitous protein whose specific functions are probably crucial to establishing its pathogenic role. Apart from its involvement in transcription, splicing and mRNA stability, TDP-43 has also been described as a Drosha-associated protein. However, our knowledge of the role of TDP-43 in the microRNA (miRNA) synthesis pathway is limited to the association mentioned above. Here we report for the first time which changes occur in the total miRNA population following TDP-43 knockdown in culture cells. In particular, we have observed that let-7b and miR-663 expression levels are down- and upregulated, respectively. Interestingly, both miRNAs are capable of binding directly to TDP-43 in different positions: within the miRNA sequence itself (let-7b) or in the hairpin precursor (miR-663). Using microarray data and real-time PCR we have also identified several candidate transcripts whose expression levels are selectively affected by these TDP-43,miRNA interactions. [source]


Ancestral roles of eukaryotic frataxin: mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologues in trypanosomes

MOLECULAR MICROBIOLOGY, Issue 1 2008
Shaojun Long
Summary Frataxin is a small conserved mitochondrial protein; in humans, mutations affecting frataxin expression or function result in Friedreich's ataxia. Much of the current understanding of frataxin function comes from informative studies with yeast models, but considerable debates remain with regard to the primary functions of this ubiquitous protein. We exploit the tractable reverse genetics of Trypanosoma brucei in order to specifically consider the importance of frataxin in an early branching lineage. Using inducible RNAi, we show that frataxin is essential in T. brucei and that its loss results in reduced activity of the marker Fe,S cluster-containing enzyme aconitase in both the mitochondrion and cytosol. Activities of mitochondrial succinate dehydrogenase and fumarase also decreased, but the concentration of reactive oxygen species increased. Trypanosomes lacking frataxin also exhibited a low mitochondrial membrane potential and reduced oxygen consumption. Crucially, however, iron did not accumulate in frataxin-depleted mitochondria, and as T. brucei frataxin does not form large complexes, it suggests that it plays no role in iron storage. Interestingly, RNAi phenotypes were ameliorated by expression of frataxin homologues from hydrogenosomes of another divergent protist Trichomonas vaginalis. Collectively, the data suggest trypanosome frataxin functions primarily only in Fe,S cluster biogenesis and protection from reactive oxygen species. [source]


Crystal structures of oxidized and reduced forms of human mitochondrial thioredoxin 2

PROTEIN SCIENCE, Issue 10 2005
Aude Smeets
ASK1, apoptosis signal-regulating kinase 1; TXN, thioredoxin; hTXN1, human cytosolic/nuclear thioredoxin 1; hTXN2, human mitochondrial thioredoxin 2; hPRDX5, human peroxiredoxin 5. Gene symbols in this article follow standard nomenclature defined by the Human Genome Organization Nomenclature Committee (http://www.gene.ucl.ac.uk/nomenclature/). For this reason TXN is used instead of the commonly used Trx for designating thioredoxin in the literature. Abstract Mammalian thioredoxin 2 is a mitochondrial isoform of highly evolutionary conserved thioredoxins. Thioredoxins are small ubiquitous protein,disulfide oxidoreductases implicated in a large variety of biological functions. In mammals, thioredoxin 2 is encoded by a nuclear gene and is targeted to mitochondria by a N-terminal mitochondrial presequence. Recently, mitochondrial thioredoxin 2 was shown to interact with components of the mitochondrial respiratory chain and to play a role in the control of mitochondrial membrane potential, regulating mitochondrial apoptosis signaling pathway. Here we report the first crystal structures of a mammalian mitochondrial thioredoxin 2. Crystal forms of reduced and oxidized human thioredoxin 2 are described at 2.0 and 1.8 Å resolution. Though the folding is rather similar to that of human cytosolic/nuclear thioredoxin 1, important differences are observed during the transition between the oxidized and the reduced states of human thioredoxin 2, compared with human thioredoxin 1. In spite of the absence of the Cys residue implicated in dimer formation in human thioredoxin 1, dimerization still occurs in the crystal structure of human thioredoxin 2, mainly mediated by hydrophobic contacts, and the dimers are associated to form two-dimensional polymers. Interestingly, the structure of human thioredoxin 2 reveals possible interaction domains with human peroxiredoxin 5, a substrate protein of human thioredoxin 2 in mitochondria. [source]


Update on peptidylarginine deiminases and deimination in skin physiology and severe human diseases

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2007
M.-C. Méchin
Synopsis Deimination (or citrullination) is a recently described post-translational modification, but its consequences are not yet well understood. It is catalysed by peptidylarginine deiminases (PADs). These enzymes transform arginyl residues involved in a peptidyl link into citrullyl residues in a calcium-dependent manner. Several PAD substrates have already been identified like filaggrin and keratins K1 and K10 in the epidermis, trichohyalin in hair follicles, but also ubiquitous proteins like histones. PADs act in a large panel of physiological functions as cellular differentiation or gene regulation. It has been suggested that deimination plays a role in many major diseases such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease and psoriasis. Five human genes (PADIs), encoding five highly conserved paralogous enzymes (PAD1-4 and 6), have been characterized. These genes are clustered in a single locus, at 1p35-36 in man. Only PAD1-3 are expressed in human epidermis. PADs seem to be controlled at transcriptional, translational and activity levels and they present particular substrate specificities. In this review, we shall discuss these main biochemical, genetic and functional aspects of PADs together with their pathophysiological implications. Résumé La désimination (ou citrullination) est une modification post-traductionnelle catalysée par les peptidyl-arginine désiminases (PADs), décrite depuis peu et dont les conséquences sont encore mal comprises. Ces enzymes transforment, de façon dépendante du calcium, les résidus arginyl engagés dans un lien peptidique en résidus citrullyl. Plusieurs substrats ont été identifiés: la filaggrine et les cytokératines K1 et K10 de l'épiderme, la trichohyaline dans le follicule pileux mais aussi des protéines ubiquistes comme les histones. Les PADs interviennent dans de nombreuses fonctions physiologiques telles que la différenciation cellulaire ou la régulation génique. La désimination pourrait jouer un rôle dans plusieurs maladies sévères et fréquentes comme la polyarthrite rhumatoïde, la sclérose en plaque, la maladie d'Alzheimer ou encore le psoriasis. Cinq gènes humains (PADIs) codant pour 5 enzymes paralogues conservées (PAD1-4 et 6) ont été caractérisés. Ils sont regroupés en un seul locus, en 1p35-36 chez l'homme. Seules les PAD1-3 sont exprimées dans l'épiderme humain. Les PADs semblent contrôlées aux niveaux transcriptionnel et traductionnel, ainsi qu'au niveau de leur activité. Elles présentent chacune leurs spécificités de substrats. Ces principaux aspects biochimiques, génétiques et fonctionnels des PADs tout comme leurs implications physiopathologiques seront discutés dans cette revue. [source]


Structure of native laccase from Trametes hirsuta at 1.8,Å resolution

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2009
Konstantin M. Polyakov
This paper describes the structural analysis of the native form of laccase from Trametes hirsuta at 1.8,Å resolution. This structure provides a basis for the elucidation of the mechanism of catalytic action of these ubiquitous proteins. The 1.8,Å resolution native structure provided a good level of structural detail compared with many previously reported laccase structures. A brief comparison with the active sites of other laccases is given. [source]


Expression, purification and X-ray crystallographic analysis of thioredoxin from Streptomyces coelicolor

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2005
Petra Stefankova
Thioredoxins are ubiquitous proteins that serve as reducing agents and general protein disulfide reductases. In turn, they are reduced by electrons obtained from the NADPH-containing thioredoxin reductase. Thioredoxins have been isolated and characterized from a large number of organisms. The Gram-positive bacterium Streptomyces coelicolor contains three thioredoxins that are involved in unknown biological processes. trxA from S. coelicolor was cloned and expressed in Escherichia coli and the protein purified and crystallized using the hanging-drop method of vapour diffusion. The crystal structure of thioredoxin A has been determined at 1.5,Å resolution using a synchrotron-radiation source. The protein reveals a thioredoxin-like fold with a typical CXXC active site. The crystal exhibits the symmetry of space group P21212, with unit-cell parameters a = 43.6, b = 71.8, c = 33.2,Å. [source]