https://scholars.lib.ntu.edu.tw/handle/123456789/568053
標題: | Molecular quality control machinery contributes to the leukocyte NADPH oxidase deficiency in chronic granulomatous disease | 作者: | Lin S.-J. Huang Y.-F. Chen J.-Y. Heyworth P.G. Noack D. Wang J.-Y. Lin C.-Y. BOR-LUEN CHIANG Yang C.-M. Liu C.-C. Shieh C.-C. |
關鍵字: | Chaperon; Immunodeficiency; Phagocyte; Respiratory burst | 公開日期: | 2002 | 卷: | 1586 | 期: | 3 | 起(迄)頁: | 275-286 | 來源出版物: | Biochimica et Biophysica Acta - Molecular Basis of Disease | 摘要: | Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by defects in leukocyte NADPH oxidase. Various inherited defects in one of the membrane-bound components of NADPH oxidase, gp91-phox, cause X-linked (X91) CGD. Analysis of three patients with X91 CGD revealed that different mechanisms of molecular quality control lead to the common phenotype of absence of mature membrane-bound NADPH oxidase complex in leukocytes. In the first patient, aberrant intron splicing created a premature stop codon. However, the mutant mRNA was degraded prematurely, which prevented the production of truncated protein. In the second patient, a frameshift mutation with the potential to generate a gp91-phox polypeptide, with an aberrant and elongated C-terminus, led to barely detectable levels of gp91-phox, even though the reported functional domains of the protein appeared unaffected. In the third patient, a point mutation created a single amino acid change in the predicted FAD-binding site of gp91-phox. Although gp91-phox was detectable with Western blotting, no cytochrome b558 was expressed on the cell surface. These analyses showed that molecular quality control machinery plays an important role in the pathogenesis of CGD, not only in the X910 but also in the X91- form of this X-linked disease. ? 2002 Elsevier Science B.V. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-18344378423&doi=10.1016%2fS0925-4439%2801%2900106-5&partnerID=40&md5=4c8b948d46704ac8c408d9645a82e68a https://scholars.lib.ntu.edu.tw/handle/123456789/568053 |
ISSN: | 0925-4439 | DOI: | 10.1016/S0925-4439(01)00106-5 | SDG/關鍵字: | antibiotic agent; cell surface protein; flavine adenine nucleotide; genomic DNA; messenger RNA; polypeptide; reduced nicotinamide adenine dinucleotide phosphate oxidase; amino acid substitution; article; binding site; carboxy terminal sequence; case report; cell surface; clinical feature; flow cytometry; frameshift mutation; granulomatosis; human; infant; intron; leukocyte; male; molecular dynamics; pathogenesis; phenotype; point mutation; preschool child; priority journal; protein domain; protein expression; protein synthesis; reverse transcription polymerase chain reaction; RNA degradation; RNA splicing; stop codon; Western blotting; Cell Membrane; Cell Nucleus; Cytochrome b Group; Endoplasmic Reticulum; Granulomatous Disease, Chronic; Humans; Infant; Intracellular Membranes; Leukocytes; Male; Membrane Glycoproteins; Mutation; NADPH Oxidase; Point Mutation; Quality Control; RNA, Messenger |
顯示於: | 醫學系 |
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