Pectenotoxin-2 represses telomerase activity in human leukemia cells through suppression of hTERT gene expression and Akt-dependent hTERT phosphorylation

In this study, we found that pectenotoxin-2 (PTX-2) decreased cell viability and inhibited telomerase activity with downregulation of hTERT expression in human leukemia cells. PTX-2 treatment also reduced c-Myc and Sp1 gene expression and DNA binding activity. Further chromatin immunoprecipitation a...

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Bibliographic Details
Published in:FEBS letters 2008-10, Vol.582 (23-24), p.3263-3269
Main Authors: Kim, Mun-Ock, Moon, Dong-Oh, Kang, Sang-Hyuck, Heo, Moon-Soo, Choi, Yung Hyun, Jung, Jee Hyung, Lee, Jae-Dong, Kim, Gi-Young
Format: Article
Language:English
Subjects:
Akt
Apoptosis
c-Myc
Cell Line, Tumor
Cell Proliferation - drug effects
ChIP
Chromatin Immunoprecipitation
DNA repair enzyme poly-(ADP-ribose) polymerase
ELISA
enzyme-linked immunosorbent assay
Furans - pharmacology
Gene Expression - drug effects
hTERT
Humans
Leukemia - metabolism
PARP
Pectenotoxin-2
Phosphorylation - drug effects
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-myc - metabolism
PTX-2
Pyrans - pharmacology
Sp1
Sp1 Transcription Factor - metabolism
Telomerase - antagonists & inhibitors
Telomerase - genetics
telomeric repeat amplification protocol
TRAP
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Summary:In this study, we found that pectenotoxin-2 (PTX-2) decreased cell viability and inhibited telomerase activity with downregulation of hTERT expression in human leukemia cells. PTX-2 treatment also reduced c-Myc and Sp1 gene expression and DNA binding activity. Further chromatin immunoprecipitation assay demonstrated that PTX-2 attenuated the binding of c-Myc and Sp1 to the regulatory regions of hTERT. We also observed that PTX-2 treatment attenuated the phosphorylation of Akt, thereby reducing the phosphorylation and nuclear translocation of hTERT. We concluded that PTX-2 suppressed telomerase activity through the transcriptional and post-translational suppression of hTERT and this process precedes cellular differentiation of human leukemia cells. MINT-6742762:hTERT (uniprotkb:O14746) physically interacts (MI:0218) with AKT (uniprotkb:P31749) by anti bait coimmunoprecipitation (MI:0006)
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2008.08.030