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A NF-?B p65 subunitis indispensable foractivating manganesesuperoxide: Dismutasegene transcriptionmediated by tumornecrosis factor-? Kayoko MaeharaTadao HasegawaKen‐ichi Isobe2000 год

A NF-?B p65 subunit is indispensable for activating manganese superoxide: Dismutase gene transcription mediated by tumor necrosis factor-?
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Аннотация: Expression of the manganese superoxide dismutase (Mn-SOD) is induced by tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and lipopolysaccharide (LPS). Recently, a TNF-responsive element (TNFRE) was identified within the second intron of the murine Mn-SOD gene. The 5′ CCAAT/enhancer binding protein (C/EBP)-related region within the TNFRE was responsive to TNF, whereas the 3′ NF-κB-related region alone was not. This report describes the minimal promoter region of the Mn-SOD gene and investigates the cis-acting elements and trans-acting factors responsible for TNF-α-induced Mn-SOD gene expression. Reporter plasmid transfection studies demonstrated that inducible transcription factors enhanced the transcriptional activity of the Mn-SOD gene through the intronic enhancer region. Electrophoretic mobility shift assays demonstrated that after TNF-α stimulation, p50 and p65 NF-κB subunits bound specifically to the newly identified NF-κB transcription factor-binding site, distinct from the previously described NF-κB site, within the intronic enhancer region. In addition, site-directed mutagenesis and cotransfection studies demonstrated that the NF-κB p65 subunit enhanced the transcriptional activity of the Mn-SOD gene through the newly identified NF-κB site. These results show that a NF-κB p65 subunit is mainly involved in the molecular mechanisms controlling TNF-α-mediated Mn-SOD gene transcription. J. Cell. Biochem. 77:474–486, 2000. © 2000 Wiley-Liss, Inc.
Год издания: 2000
Авторы: Kayoko Maehara, Tadao Hasegawa, Ken‐ichi Isobe
Издательство: Wiley
Источник: Journal of Cellular Biochemistry
Ключевые слова: NF-κB Signaling Pathways, Immune Response and Inflammation, Peroxisome Proliferator-Activated Receptors
Другие ссылки: Journal of Cellular Biochemistry (HTML)
PubMed (HTML)