Identification of two distinct elements mediating activation of telomerase (hTERT) gene expression in association with cell growth in human T cells.
Lymphocytes are exceptional among normal somatic cells in that they express high telomerase activity like germline and malignant cells. We investigated the induction of telomerase in human T cells in association with cell growth. IL-2 significantly augmented the expression of mRNA for human telomerase reverse transcriptase (hTERT), a rate-limiting component of telomerase, in PHA-activated human peripheral blood leukocytes. An isolated 5'-flanking sequence (-3927-+51) of the hTERT gene was examined for its promoter activity in an IL-2-dependent human T cell line Kit 225. Addition of IL-2 into quiescent Kit 225 cells induced activation of the hTERT promoter. Reporter assays with mutant fragments of the hTERT promoter further revealed that IL-2-dependent activation was independently mediated by two elements within the +9-+51 regions. The two elements showed similar kinetics of activation in response to IL-2, which coincided with the G1 to S phase transition of the cell cycle. Interestingly, introduction of mutation in the elements increased background promoter activities in resting T cells in the absence of IL-2. Our results demonstrate that the hTERT promoter may be suppressed by the elements and IL-2 may signal for de-suppression in association with promotion of cell growth. IL-2-dependent activation of the hTERT promoter may be necessary for prevention from senescence induced by extraordinary cell division during immune reactions.
Matsumura-Arioka
Yuuki
Y
Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Ohtani
Kiyoshi
K
Hara
Toshifumi
T
Iwanaga
Ritsuko
R
Nakamura
Masataka
M
D001483:Base Sequence; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D012333:RNA, Messenger; D019098:Telomerase