Variant forms of upstream stimulatory factors (USFs) control the promoter activity of hTERT, the human gene encoding the catalytic subunit of telomerase.
It is known that Myc regulates the expression of TERT, the telomerase catalytic subunit gene, by binding to E box. Here we show that another E box-binding protein, upstream stimulatory factor (USF), also regulates TERT expression. Specifically, the N-terminally truncated form of USF2 is present in telomerase-negative/resting human lymphocytes, but not in telomerase-positive/phytohemagglutinin-activated lymphocytes. In electrophoretic mobility shift assay, both full-length and truncated USF2s bound to the TERT E box. In a transient expression assay, the truncated USF had a dominant-negative effect on both exogenous full-length USF and endogenous positive regulators for activating TERT expression. These results suggest that the differential abundance of truncated USF2 may regulate telomerase activity during lymphocyte activation.
Yago
Masako
M
Laboratory of Molecular and Cellular Assembly, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Ohki
Rieko
R
Hatakeyama
Shinji
S
Fujita
Toshiro
T
Ishikawa
Fuyuki
F
D001665:Binding Sites; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D004247:DNA; C509186:TERT protein, human; D019098:Telomerase