3-Deazaadenosine, aS-Adenosylhomocysteine Hydrolase Inhibitor, Has Dual Effects on NF-κB Regulation

Seong-Yun Jeong, Sang-Gun Ahn, Jeong-Hwa Lee, Ho-Shik Kim, Jin-Woo Kim, Hyangshuk Rhim, Seong-Whan Jeong, In-Kyung Kim
1999 Journal of Biological Chemistry  
Previously we reported that 3-deazaadenosine (DZA), a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase inhibits bacterial lipopolysaccharideinduced transcription of tumor necrosis factor-␣ and interleukin-1␤ in mouse macrophage RAW 264.7 cells. In this study, we demonstrate the effects of DZA on nuclear factor-B (NF-B) regulation. DZA inhibits the transcriptional activity of NF-B through the hindrance of p65 (Rel-A) phosphorylation without reduction of its nuclear
more » ... n and DNA binding activity. The inhibitory effect of DZA on NF-B transcriptional activity is potentiated by the addition of homocysteine. Taken together, DZA promotes the proteolytic degradation of IB␣, but not IB␤, resulting in an increase of DNA binding activity of NF-B in the nucleus in the absence of its transcriptional activity in RAW 264.7 cells. The reduction of IB␣ by DZA is neither involved in IB kinase complex activation nor modulated by the addition of homocysteine. This study strongly suggests that DZA may be a potent drug for the treatment of diseases in which NF-B plays a central pathogenic role, as well as a useful tool for studying the regulation and physiological functions of NF-B.
doi:10.1074/jbc.274.27.18981 pmid:10383397 fatcat:k3ogqi6agfg2dnf7d3l45xuuzy