NF-kappa B 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-kappaB 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-kappaB 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-kappaB consensus oligonucleotide; 2) protein binding to this site was enhanced by NF-kappaB activators tumor necrosis factor-alpha, phorbol 12-myristate 13-acetate, and interleukin-1beta; and 3) the complex was specific and could be supershifted with antibodies against the p50 or p65 NF-kappaB subunits. The NF-kappaB 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-kappaB site could also be enhanced by co-transfection with an NF-kappaB1 expression vector. NF-kappaB may therefore contribute to the activation of TERT expression observed in mouse tissue.
Yin
L
L
Department of Molecular and Cell Biology and the Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, USA.
Hubbard
A K
AK
Giardina
C
C
D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain / Q000235:genetics; D004247:DNA / Q000378:metabolism; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D016328:NF-kappa B; D004247:DNA; D019098:Telomerase