A major role of PKC theta and NFkappaB in the regulation of hTERT in human T lymphocytes.
Expression of the telomerase catalytic subunit (TERT) is the rate-limiting determinant of telomerase activity in most human cells. In this work, we examined the participation of protein kinase C (PKC) in the regulation of hTERT expression in human T lymphocytes. Transient expression assays using luciferase reporter plasmids containing hTERT promoter showed that overexpression of PKC theta, but not the other PKC isoforms, could activate the promoter activity of hTERT in resting T lymphocytes. Among the PKC theta-activated signalings, we presented evidence that the expression of hTERT is mediated through NFkappaB but not through MEK or c-Jun N-terminal kinase pathways. Analysis of the hTERT promoter occupancy in vivo using chromatin immunoprecipitation assays, however, did not detect an increased binding of NFkappaB to the hTERT promoter in the activated T cells, although an increased binding of cMyc and Sp1 was detected. Together with the observation that inhibition of NFkappaB eliminated the induction of cMyc in activated T cells, these results suggest that PKC theta-activated NFkappaB signaling regulates the expression of hTERT via cMyc in human T lymphocytes.
Sheng
Wei-Yun
WY
Department of Molecular and Cellular Biology, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan.
Chen
Yi-Ru
YR
Wang
Tzu-Chien V
TC
D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D011493:Protein Kinase C; C509186:TERT protein, human; D019098:Telomerase