Directed mutagenesis in region 713-720 of human thyroperoxidase assigns 713KFPED717 residues as being involved in the B domain of the discontinuous immunodominant region recognized by human autoantibodies.
AuthorsBresson D, Pugnière M, Roquet F, Rebuffat SA, N-Guyen B, Cerutti M, Guo J, McLachlan SM, Rapoport B, Estienne V, Ruf J, Chardès T, Péraldi-Roux S,
JournalJ Biol Chem
PubMed ID15150267
'Autoantibodies (aAbs) to thyroid peroxidase (TPO), the hallmark of autoimmune thyroid disease (AITD), recognize conformational epitopes restricted to an immunodominant region (IDR), divided into two overlapping domains A and B. Despite numerous efforts aimed at localizing the IDR and identifying aAb-interacting residues on TPO, only two critical amino acids, Lys(713) ... More
Does mPER2 protein oscillate without its coding mRNA cycling?: post-transcriptional regulation by cell clock.
AuthorsFujimoto Y, Yagita K, Okamura H,
JournalGenes Cells
PubMed ID16629904
'Does the mammalian oscillatory protein mPER2 show the rhythm without its coding mRNA cycling? Here we answer this question by inserting a single copy of exogenous mPer2 gene to a NIH3T3 fibroblasts cell line, using Flp-In system. We generated the stable cell lines which constantly express mRNAs coding either N-terminal ... More
Unlike Diablo/smac, Grim promotes global ubiquitination and specific degradation of X chromosome-linked inhibitor of apoptosis (XIAP) and neither cause apoptosis.
AuthorsSilke J, Kratina T, Ekert PG, Pakusch M, Vaux DL,
JournalJ Biol Chem
PubMed ID14570909
'Grim is a Drosophila inhibitor of apoptosis (IAP) antagonist that directly interferes with inhibition of caspases by IAPs. Expression of Grim, or removal of DIAP1, is sufficient to activate apoptosis in fly cells. Transient expression of Grim in mammalian cells induces apoptosis, arguing for the conservation of apoptotic pathways, but ... More
Genetic analysis of the herpes simplex virus type 1 UL20 protein domains involved in cytoplasmic virion envelopment and virus-induced cell fusion.
AuthorsMelancon JM, Foster TP, Kousoulas KG,
JournalJ Virol
PubMed ID15220406
'The herpes simplex virus type 1 UL20 protein (UL20p) is an important determinant for cytoplasmic virion morphogenesis and virus-induced cell fusion. To delineate the functional domains of the UL20 protein, we generated a panel of single and multiple (cluster) alanine substitutions as well as UL20p carboxyl-terminal truncations. The UL20 mutant ... More
Localization of the discontinuous immunodominant region recognized by human anti-thyroperoxidase autoantibodies in autoimmune thyroid diseases.
'The discontinuous immunodominant region (IDR) recognized by autoantibodies directed against the thyroperoxidase (TPO) molecule, a major autoantigen in autoimmune thyroid diseases, has not yet been completely localized. By using peptide phage-displayed technology, we identified three critical motifs, LXPEXD, QSYP, and EX(E/D)PPV, within selected mimotopes which interacted with the human recombinant ... More
Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells.
'NOD2, a cytosolic receptor for the bacterial proteoglycan fragment muramyl dipeptide (MDP), plays an important role in the recognition of intracellular pathogens. Variants in the bacterial sensor domain of NOD2 are genetically associated with an increased risk for the development of Crohn disease, a human chronic inflammatory bowel disease. In ... More
GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism.
'Sialic acid is a major determinant of carbohydrate-receptor interactions in many systems pertinent to human health and disease. N-Acetylmannosamine (ManNAc) is the first committed intermediate in the sialic acid biosynthetic pathway; thus, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid production. UDP-GlcNAc 2-epimerase and GlcNAc ... More
Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor.
AuthorsHemming ML, Selkoe DJ,
JournalJ Biol Chem
PubMed ID16154999
'Human genetic data have associated angiotensin-converting enzyme (ACE) with Alzheimer disease (AD), and purified ACE has been reported to cleave synthetic amyloid beta-protein (Abeta) in vitro. Whether deficiency in ACE activity, arising from genetic alteration or pharmacological inhibition, can decrease Abeta degradation and allow Abeta accumulation in intact cells is ... More
Stable transmission of targeted gene modification using single-stranded oligonucleotides with flanking LNAs.
AuthorsAndrieu-Soler C, Casas M, Faussat AM, Gandolphe C, Doat M, Tempé D, Giovannangeli C, Behar-Cohen F, Concordet JP,
JournalNucleic Acids Res
PubMed ID16002788
Targeted mutagenesis directed by oligonucleotides (ONs) is a promising method for manipulating the genome in higher eukaryotes. In this study, we have compared gene editing by different ONs on two new target sequences, the eBFP and the rd1 mutant photoreceptor betaPDE cDNAs, which were integrated as single copy transgenes at ... More
Acylation of CD44 and its association with lipid rafts are required for receptor and hyaluronan endocytosis.
AuthorsThankamony SP, Knudson W,
JournalJ Biol Chem
PubMed ID16945930
CD44 is a cell surface receptor for the extracellular matrix macromolecule hyaluronan. In addition, CD44 mediates the endocytosis of hyaluronan leading to its subsequent degradation within lysosomes. Using model systems of COS-7 and Flp-293 cells, we demonstrate that the association of CD44 with lipid rafts is essential for the endocytosis ... More
Mevalonate kinase is a cytosolic enzyme in humans.
In the past decade several reports have appeared which suggest that peroxisomes play a central role in isoprenoid/cholesterol biosynthesis. These suggestions were based primarily on the reported finding of several of the enzymes of the presqualene segment of the biosynthetic pathway in peroxisomes. More recently, however, conflicting results have been ... More
Dual oxidase2 is expressed all along the digestive tract.
AuthorsEl Hassani RA, Benfares N, Caillou B, Talbot M, Sabourin JC, Belotte V, Morand S, Gnidehou S, Agnandji D, Ohayon R, Kaniewski J, Noël-Hudson MS, Bidart JM, Schlumberger M, Virion A, Dupuy C,
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID15591162
The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and ... More
A mutation in the cystic fibrosis transmembrane conductance regulator generates a novel internalization sequence and enhances endocytic rates.
Cystic fibrosis is a common lethal genetic disease among Caucasians. The cystic fibrosis gene encodes a cyclic adenosine monophosphate-activated chloride channel (cystic fibrosis transmembrane conductance regulator (CFTR)) that mediates electrolyte transport across the luminal surfaces of a variety of epithelial cells. Mutations in CFTR fall into two broad categories; those ... More
Generation of soluble leptin receptor by ectodomain shedding of membrane-spanning receptors in vitro and in vivo.
AuthorsGe H, Huang L, Pourbahrami T, Li C,
JournalJ Biol Chem
PubMed ID12270921
Leptin is an adipocyte-derived hormone with potent effects on food intake and body weight. Genetically obese rodents with mutations of leptin or leptin receptor develop morbid obesity and diabetes. The receptor for leptin, OB-R, is alternatively spliced to at least five transcripts, encoding receptors designated OB-Ra, -b, -c, -d, and ... More
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy.
AuthorsNarendra D, Tanaka A, Suen DF, Youle RJ,
JournalJ Cell Biol
PubMed ID19029340
Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease. Although the role of Parkin in neuron maintenance is unknown, recent work has linked Parkin to the regulation of mitochondria. Its loss is associated with swollen mitochondria and muscle ... More