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Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells
Karolinska Hosp, Hematol Lab, CMM, Radiumhemmet,Dept Med,Div Hematol, SE-17176 Stockholm, Sweden Karolinska Hosp, Radiumhemmet, Dept Oncol, SE-17176 Stockholm, Sweden Karolinska Inst, Ctr Microbiol & Tumor Biol, SE-17177 Stockholm, Sweden Stockholm Univ, Dept Biochem, SE-10405 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, SE-58185 Linkoping, Sweden.
Karolinska Hosp, Hematol Lab, CMM, Radiumhemmet,Dept Med,Div Hematol, SE-17176 Stockholm, Sweden Karolinska Hosp, Radiumhemmet, Dept Oncol, SE-17176 Stockholm, Sweden Karolinska Inst, Ctr Microbiol & Tumor Biol, SE-17177 Stockholm, Sweden Stockholm Univ, Dept Biochem, SE-10405 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, SE-58185 Linkoping, Sweden.
Karolinska Hosp, Hematol Lab, CMM, Radiumhemmet,Dept Med,Div Hematol, SE-17176 Stockholm, Sweden Karolinska Hosp, Radiumhemmet, Dept Oncol, SE-17176 Stockholm, Sweden Karolinska Inst, Ctr Microbiol & Tumor Biol, SE-17177 Stockholm, Sweden Stockholm Univ, Dept Biochem, SE-10405 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, SE-58185 Linkoping, Sweden.
Karolinska Hosp, Hematol Lab, CMM, Radiumhemmet,Dept Med,Div Hematol, SE-17176 Stockholm, Sweden Karolinska Hosp, Radiumhemmet, Dept Oncol, SE-17176 Stockholm, Sweden Karolinska Inst, Ctr Microbiol & Tumor Biol, SE-17177 Stockholm, Sweden Stockholm Univ, Dept Biochem, SE-10405 Stockholm, Sweden Linkoping Univ, Fac Hlth Sci, SE-58185 Linkoping, Sweden.
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2000 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 19, no 45, 5123-5133 p.Article in journal (Refereed) Published
Abstract [en]

The p53 tumor suppressor protein inhibits the formation of tumors through induction of cell cycle arrest and/or apoptosis, In the present study we demonstrated that p53 is also a powerful inhibitor of human telomerase reverse transcriptase (hTERT), a key component for telomerase, Activation of either exogenous temperature-sensitive (ts) p53 in BL41 Burkitt lymphoma cells or endogenous wild type (wt) p53 at a physiological level in MCF-7 breast carcinoma cells triggered a rapid downregulation of hTERT mRNA expression, independently of the induction of the p53 target gene p21, Co-transfection of an hTERT promoter construct with wt p53 but not mutant p53 in HeLa cells inhibited the hTERT promoter activity. Furthermore, the activation of the hTERT promoter in Drosophila Schneider SL2 cells was completely dependent on the ectopic expression of Sp1 and was abrogated by wt p53, Finally, wt p53 inhibited Sp1 binding to the hTERT proximal promoter by forming a p53-Sp1 complex. Since activation of telomerase, widely observed in human tumor cell lines and primary tumors, is a critical step in tumorigenesis, wt p53-triggered inhibition of hTERT/telomerase expression may reflect yet another mechanism of p53-mediated tumor suppression. Our findings provide new insights into both the biological function of p53 and the regulation of hTERT/telomerase expression.

Place, publisher, year, edition, pages
2000. Vol. 19, no 45, 5123-5133 p.
Keyword [en]
hTERT, p53, Sp1, telomerase
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-49548OAI: oai:DiVA.org:liu-49548DiVA: diva2:270444
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12

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