1 / 12

Inactivation of hTERT transcription by Tax

Inactivation of hTERT transcription by Tax. Julien Daniel, Raphael Doineau, Astrild Vaudaine, Sebastian Schmidt, Sebastian Olényi Gabet et al., Oncogene 2003. Leukemia-causing?.

eve
Download Presentation

Inactivation of hTERT transcription by Tax

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Inactivation of hTERT transcription by Tax Julien Daniel, Raphael Doineau, Astrild Vaudaine, Sebastian Schmidt, Sebastian Olényi Gabet et al., Oncogene 2003

  2. Leukemia-causing? Blood cancer- telomere dysfunctiongenerates dicentric and multicentric chromosomes- T-cell leukemia virus type1(HTLV -1) - 3–5% of infected individuals develop adultT-cell leukemia/lymphoma (ATLL) - oncoprotein Tax

  3. The idea - telomere dysfunction observed in solid tumors- E-boxes also implicated in the Tax-associatedtranscriptional inhibition of several cellular genes (p53) -> Telomerase-inactivation?

  4. Cell lysate TRAP = Telomerase Repeat Amplification Protocol Differential telomere length or quantity PCR with labelling of telomere repeats Detection (ELISA, X-ray of radioactively marked probes, ...) Amplified, marked telomeres

  5. Cell lysate TRAP = Telomerase Repeat Amplification Protocol Differential telomere length or quantity RT-PCR with telomere-primers and detection Detection of the original amount of telomere repeats from the RT-PCR-procedure

  6. Amplification measured by real-time PCR • Importance of Tax in the decrease of telomerase activity

  7. Effect of Tax on hTERT promoter-luciferase • Tax reduces luciferase activity • hTERT is repressed by Tax

  8. Discussion - Outview „Paradoxical“ role of TAX: • activates T-cell proliferation; in normal T-cells, hTERT is activated • At the same time, it blocks hTERT transcription • Thus, Tax favours chromosome rearrangement and mutation accumulation, leading to malignant cells • Tax expression is restricted to the pre-malignant stage where it inhibits the „reparatory effect“ of hTERT

  9. Discussion - Outview • Many other forms of cancer are also preceded by a long latency • There seem to exist other oncogenes exhibiting the same role as Tax • Thus, better examination of the Tax mechanism may provide insights into other forms of cancer

More Related