Disease relevance of NDUFB6

• The inserted DNA was expressed in Escherichia coli transformants as a polypeptide fused to the lambda CI protein at its amino terminus and to beta-galactosidase at its carboxyl terminus [1].
• CONCLUSION: The CI regimen was virtually identical to CIB with regard to response rate, PFS, survival, and toxicity profile [2].
• NADH dehydrogenase or complex I (CI) is affected in most of the mitochondrial diseases and in some neurodegenerative disorders [3].
• METHODS: CI secretion and steady-state pro alpha1(I) collagen messenger RNA (mRNA) levels and COL1A2 gene activation were examined in fibroblasts grown from lung biopsy specimens obtained from 16 scleroderma patients with lung fibrosis and from 10 histologically normal lung specimens (controls) [4].
• Cleavage of bacteriophage phi 80 CI repressor by RecA protein [5].

Psychiatry related information on NDUFB6

• The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus [6].

High impact information on NDUFB6

• Translocated apo B17 is strongly associated with the membrane of the ER, being only partially releasable with alkaline carbonate, and remaining bound to the microsomes following disruption with saponin [7].
• Earlier studies have suggested that an increased risk of nasopharyngeal carcinoma is associated with specific haplotypes in the HLA region: relative risks slightly over twofold were found for haplotypes A2, Bw46 and the antigen B17 [8].
• The odds ratio of the TC + TT versus CC genotype of the C242T polymorphism between control subjects and case patients was 0.49 (95% CI, 0.28 to 0.87) (P=.015) [9].
• Microcin B17: posttranslational modifications and their biological implications [10].
• The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease [6].

Biological context of NDUFB6

• The gene of the B17 subunit has been mapped to chromosome 2 [11].
• The cDNA open reading frame of B17 comprises 387 bp and encodes a protein of 128 amino acids (calculated Mr 15.5 kDa) [11].
• Molecular characterization and mutational analysis of the human B17 subunit of the mitochondrial respiratory chain complex I [11].
• At high concentrations (5-6-fold higher than the concentration necessary for 100% CI inhibition), rotenone showed a second toxic effect at the level of microtubule assembly, which also led to apoptosis [3].
• We observed a quantitative correlation between the level of CI impairment and cell respiration, cell growth, free radical production, lipid peroxidation, mitochondrial membrane potential, and apoptosis [3].

Anatomical context of NDUFB6

• Transient expression assays confirmed that genes coding for CI are transcriptionally activated in scleroderma lung fibroblasts compared with control strains [4].
• The idiotype is identified with antisera and monoclonal antibodies prepared against the IgM (kappa) antibody secreted by the Epstein-Barr virus-transformed human B cell line B17 [12].
• We have used this probe and Southern blotting techniques to identify the human apo CI gene in DNA from a series of rodent X human somatic cell hybrids [13].
• When administered orally, the CI fusion protein induced efficient immunological suppression of ovalbumin-specific T-cell responses in mice co-immunized parenterally with insulin and ovalbumin [14].
• A human-human hybridoma producing cytotoxic antibody to HLA-B15, cross-reacting with B17, B5, B35 and B18 [15].

Associations of NDUFB6 with chemical compounds

• Both culture compartments contain a large chondroitin sulfate proteoglycan (MI, CI) that eluted in the void volume of a Sepharose CL-4B column and contained glycosaminoglycan chains of molecular weight (mol wt) approximately 38,000 [16].
• Meanwhile, in vitro studies with microcin B17 have helped to uncover the molecular mechanisms by which post-translational modification results in the formation of heterocyclic oxazole and thiazole rings [17].
• Two arginine residues in positions B13 and B17 that project like forefinger and middle finger from the helix provide the electrostatic element opposed by the hydrophobic (thumb) element isoleucine (B20), offset from the arginines by about 40 degrees [18].
• Members of the B17 family share a preference for peptides with serine, threonine, or alanine at position 2 and aromatic residues at the carboxyl terminus [19].
• The derivative in which the two arginines in positions B13 and B17 had been replaced by the uncharged isosteric amino acid citrulline were biologically inactive [20].

Other interactions of NDUFB6

• Mutation analysis in three other candidate genes (beta-tropomyosin, NDUFB6 and SMU1) did not identify any mutations [21].

Analytical, diagnostic and therapeutic context of NDUFB6

• RESULTS: There were no significant differences between CI and CIB with regard to response rates (32% v 31.2%, respectively), progression-free survival (PFS), or overall survival [2].
• The HLA-B17 cross-reactive group and the participation of the subdivisions of B17 ( Bw57 and Bw58 ) in cross-reactivity were investigated by the serological analysis of 81 cytotoxic HLA antisera (produced by pregnancy alone), the HLA typing of the antiserum donors and the identification of their immunizing antigens [22].
• The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP) [23].
• Here, we report correlation of DNA typing results with serological and IEF results for the B17 group [24].
• In addition, we demonstrate that the CI fusion protein induces efficient immunosuppression after oral administration, raising the possibility of using such constructs in the treatment of type-1 diabetes [14].

References