Transforming Growth Factor β Triggers Two Independent-Senescence Programs in Cancer Cells

Katakura, Yoshinori; Nakata, Eriko; Miura, Takumi; Shirahata, Sanetaka

doi:10.1006/bbrc.1999.0129

Cited by 103 publications

(69 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A large number of studies have reported the activation mechanisms of the hTERT promoter, whereas only a few studies have reported the repression mechanisms of the hTERT promoter (Ducrest et al, 2002). We have previously reported that TGF-b can repress telomerase activity and hTERT transcription in the A549 cells (Katakura et al, 1999). In the course of our study, which aimed to clarify the molecular mechanisms underlying the hTERT repression, we found that TAK1, originally identified as an MAPKKK functioning in the TGF-b signaling pathway (Yamaguchi et al, 1995), signals to repress the hTERT transcription.…”

Section: Discussionmentioning

confidence: 96%

“…Reverse transcriptase-polymerase chain reaction hTERT and TEP1 expression were analysed by reverse transcriptase (RT)-PCR as previously described (Katakura et al, 1999). RNA was isolated with GenElute Mammalian Total RNA Miniprep kit (Sigma), and cDNA was prepared using M-MLV RT RNase H À (Promega) according to the manufacturer's protocol.…”

Section: Western Blotmentioning

confidence: 99%

“…Senescence-associated b-galactosidase (SA-b-Gal) assay SA-b-Gal assay was performed according to the method described by Dimri et al (1995;Katakura et al, 1999). Staining was performed at 371C for 12 h.…”

Section: Western Blotmentioning

confidence: 99%

“…We have previously demonstrated that transforming growth factor b (TGF-b) can repress hTERT gene expression, leading to telomere shortening in the human lung adenocarcinoma cell line, that is, A549 cells (Katakura et al, 1999). In the process of identifying the signal transduction pathway that represses the hTERT gene, we found that TGF-b-activated kinase 1 (TAK1), originally identified as a mitogen-activated kinase kinase kinase (MAPKKK) that functions in the TGF-b signaling pathway (Yamaguchi et al, 1995), triggers signals to repress the hTERT promoter.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

TAK1 represses transcription of the human telomerase reverse transcriptase gene

et al. 2007

View full text Add to dashboard Cite

In human cells, telomerase activity is tightly regulated by the expression of its catalytic subunit, namely, the human telomerase reverse transcriptase (hTERT). However, the molecular mechanisms involved in the regulation of hTERT expression have not been completely clarified. We have previously reported that transforming growth factor b (TGF-b) represses the expression of the hTERT gene. In the present study, we demonstrated that TGF-bactivated kinase 1 (TAK1), originally identified as a mitogen-activated kinase kinase kinase, represses the hTERT core promoter activity in an E-box-independent manner, and it also represses the transcription of the hTERT gene in human lung adenocarcinoma cell line, A549 cells. This TAK1-induced repression was found to be caused by the recruitment of histone deacetylase to Sp1 at the hTERT promoter and a consequent reduction in the amount of acetylated histone H4 at the hTERT promoter. Finally, we demonstrated that TAK1 induces cellular senescence programs in normal human diploid cells. Thus, we assume that TAK1 triggers the repression mechanisms of the hTERT gene as a result of evoking cellular senescence programs. Considered together, TAK1 is thought to play a causative role in the determination of a finite replicative lifespan of normal and cancer cells.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Western Blotmentioning

confidence: 99%

Section: Western Blotmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TAK1 represses transcription of the human telomerase reverse transcriptase gene

et al. 2007

View full text Add to dashboard Cite

show abstract

“…With profound anti-proliferative effects on a variety of cell types, including several types of tumor cells [3,4], the anti-proliferative effects of TGF-β have been reported to be primarily mediated through the up-regulation of cell cycle inhibitors such as p15 INK4b and p21 CIP1 , and down-regulation of cell cycle stimulators such as c-myc and cyclin-dependent kinases 4 and 6 ( Figure 1). Concomitantly TGF-β may up-regulate the cyclin-dependent kinase inhibitors p15 INK4b and p21 CIP1 by both Smad directed transcriptional activation and indirect release of repression by c-myc.…”

Section: Tgf-β Signalingmentioning

confidence: 99%