Fanconi anemia (FA), an inherited disease, is associated with progressive bone marrow failure, predisposition to cancer, and genomic instability. Genes corresponding to 15 identified FA complementation groups have been cloned, and each gene product functions in the response to DNA damage induced by cross-linking agents and/or in protection against genome instability. Interestingly, overproduction of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and aberrant activation of NF-κB-dependent transcriptional activity have been observed in FA cells. Here we demonstrated that FANCD2 protein inhibits NF-κB activity in its monoubiquitination-dependent manner. Furthermore, we detected a specific association between FANCD2 and an NF-κB consensus element in the TNF-α promoter by electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assay. Therefore, we propose FANCD2 deficiency promotes transcriptional activity of the TNF-α promoter and induces overproduction of TNF-which then sustains prolonged inflammatory responses. These results also suggest that artificial modulation of TNFα production could be a promising therapeutic approach to FA.
Terminal olefins can be converted into the corresponding sulfonates by sulfonation with SO3 followed by hydrolysis, the products are used as detergent ingredients. Although internal olefins were also expected to be good feed stocks, it was difficult to convert them into the corresponding sulfonates with as good of a yield as that of terminal olefins under the same synthesis conditions. Our studies have been carried out in order to clarify the reason for poorer conversion of the internal olefins. It was found by a nuclear magnetic resonance spectroscopic study that the major components of the sulfonated intermediate of internal olefins were /~-sultones, the amounts of which were usually very small in sulfonated terminal olefins. A portion of these/3-sultones was desulfonated, depending on temperature, to the original olefins and the corresponding sulfate salts during alkaline hydrolysis. The prevention of desulfonation of the ~sultones in the hydrolysis process was one of the most important aspects for the production of internal olefin sulfonates.Finally, by keeping the hydrolysis temperature below 35°C, the conversion of internal olefins into sulfonates was achieved with the same yield as that of conventional terminal olefins.KEY WORDS: a~Olefin, a~olefin sulfonate, alkenesulfonate, AOS, f~ sultone, carbyl sulfate, desulfonation, y-sultone, hydroxyalkanesulfonate, internal olefin sulfonate.
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