1 / 13

TAIP induces apoptosis in hepatocellular carcinoma-derived cells

TAIP induces apoptosis in hepatocellular carcinoma-derived cells. Klaas Kooistra Biological Chemistry, Molecular Genetics LIC, Leiden University LC Workshop Proteins killing Tumour Cells November 1, 2007. Menu. A specific TT virus strain has a CAV-like genome

tiana
Download Presentation

TAIP induces apoptosis in hepatocellular carcinoma-derived cells

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. TAIP induces apoptosis in hepatocellular carcinoma-derived cells Klaas Kooistra Biological Chemistry, Molecular Genetics LIC, Leiden University LC Workshop Proteins killing Tumour Cells November 1, 2007

  2. Menu • A specific TT virus strain has a CAV-like genome • TTV protein (TAIP) harbors apoptin-like characteristics? • Amino-acid sequence similarities? • Apoptosis? • TAIP-studies in human tumor cell lines

  3. Specific TT virus (TTV) strain • TT viruses belong to human circoviridae • Single stranded circular DNA virus • Within TT viruses a very high genetic variability exists • TTV strain (GenBank: AB008394) described by Miyata • Isolated from Japanese patient with non-A-E hepatitis • Attracted our specific attention for …..

  4. GC-rich region SP-1 site Poly(A) site TATA box TTV-strain has CAV-like genomic organization TAIP Apoptin TTV: torque teno virus CAV: chicken anemia virus Miyata et al. 1999

  5. TAIP Apt TAIP Apt TAIP Apt TAIP amino acid sequence shows “similarities” with apoptin’s Hydrophobic a.a. stretches; Proline distribution; Thr/Ser-rich

  6. 15 kD Expression of TAIP in human tumor cells Putative TTV-derived TAIP of 105 a.a. Approach 0.36 kb Myc-TAIP DNA was synthesized (Midland, USA) Cloned in pCMV-expression vector TAIP production in COS-1 cells

  7. TAIP Cytoplasmic TAIP induces apoptosis in HUH-7 cells TAIP DNA apoptin apoptin DNA IFA / HUH-7 cells

  8. 5 days post transfection TAIP Apoptin Lac Z TAIP induces apoptosis human HCC cells Transient transfection of three human hepatocellular carcinoma (HCC) cell lines

  9. 5 days post transfection TAIP Apoptin Lac Z TAIP induces much less apoptosis in non-HCC Transient transfection of three non-HCC cell lines

  10. TAIP Apoptin Lac Z TAIP-induces apoptosis in HCC significantly more than in non-HCC Preliminary results: TAIP does not induce apoptosis in normal rat hepatocytes

  11. Conclusions TAIP induces p53 independent apoptosis TAIP induces apoptosis preferentially in HCC cells TAIP is localized in the cytoplasm in cancer cells TAIP non-toxic for normal cells (?) TAIP functions differently than apoptin?!

  12. Acknowledgements Ying-Hui Zhang Niek Hendriquez Bertram Weiss Dominik Mumberg Mathieu Noteborn Thank you for your attention

  13. Literature of interest • Miyata et al., Identification of a novel GC-rich 113-nucleotide region to complete the circular, single-stranded DNA genome of TT virus, the first human circovirus.J Virol. 1999 May;73(5):3582-6. • Kooistra et al., TT virus-derived apoptosis-inducing protein induces apoptosis preferentially in hepatocellular carcinoma-derived cells.J Gen Virol. 2004 Jun;85(Pt 6):1445-50. • Hino and Miyata, Torque teno virus (TTV): current status.Rev Med Virol. 2007 Jan-Feb;17(1):45-57.

More Related