NF-κB Regulates Transcription of the Mouse Telomerase Catalytic Subunit

Expression of the telomerase catalytic subunit (TERT) is the rate-limiting determinant of telomerase activity in most cells. Analysis of the mouse TERT promoter revealed a potential NF-κB binding site 350 base pairs upstream from the translational start site. An oligonucleotide from this region of the TERT promoter bound to proteins in a nuclear extract prepared from a mouse hepatoma cell line. These proteins were identified as NF-κB by a number of criteria: 1) the protein complex formed on the TERT oligonucleotide had an electrophoretic mobility similar to that formed on an NF-κB consensus oligonucleotide; 2) protein binding to this site was enhanced by NF-κB activators tumor necrosis factor-α, phorbol 12-myristate 13-acetate, and interleukin-1β; and 3) the complex was specific and could be supershifted with antibodies against the p50 or p65 NF-κB subunits. The NF-κB binding site from the mouse TERT promoter activated transcription when fused to a basal SV40 promoter and enhanced the activity of the native TERT promoter in mouse hepatoma cells stimulated with phorbol 12-myristate 13-acetate. Transcriptional activation by the TERT NF-κB site could also be enhanced by co-transfection with an NF-κB1 expression vector. NF-κB may therefore contribute to the activation of TERT expression observed in mouse tissue.