The role of a single-stranded nucleotide loop in transcriptional regulation of the human sod2 gene.

Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is necessary for survival of aerobic life. Previously, we demonstrated that a Sp1-based promoter is essential for constitutive transcription and a NF-kappaB-based intronic enhancer is responsible for cytokine-mediated induction. Here we show that nucleophosmin (NPM), a RNA-binding protein, binds to an 11G single-stranded loop in the promoter region and serves to integrate the Sp1 and NF-kappaB responses. Disruption of the loop structure causes a reduction of both constitutive and inductive transcription due to loss of the binding motif for NPM. Interaction of NF-kappaB.NPM.Sp1 facilitated by binding of NPM to the loop structure in the promoter region appears to comprise the basic complex for the transcriptional stimulation. These results suggest a novel molecular mechanism for communication between the enhancer and the GC-rich promoter.