Apoptin

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Apoptin

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Author : Astrid Adriana Anna Maria Danen-van Oorschot
language : en
Publisher:
Release Date : 2001

Apoptin written by Astrid Adriana Anna Maria Danen-van Oorschot and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001 with categories.

Signalling For Cell Death By Apoptin A Tumor Specific Apoptosis Inducer

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Author : Patrayu Taebunpakul
language : en
Publisher:
Release Date : 2012

Signalling For Cell Death By Apoptin A Tumor Specific Apoptosis Inducer written by Patrayu Taebunpakul and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with Apoptosis categories.

Apoptin, a protein derived from chicken anaemia virus, has been reported to induce cell death in cancer cells but not in normal cells. The mechanism of apoptin-induced apoptosis is not clearly understood. However, it is likely to act through the intrinsic death pathway and independently of p53. In most cancers, p53 is mutated while its family member p73, which has similar functions, is rarely affected. Therefore, in this thesis, the mechanism of apoptin-induced apoptosis through the p73 pathway was investigated. -- Apoptin expression in cancer cells leads to an increase in TAp73[alpha] levels suggesting the involvement of the p73 pathway in apoptin-induced apoptosis. Using knockdown/knockout experiments the direct roles of p53 and p73 as well as p73 protein modulators in cell death induced by apoptin was investigated. The results showed that apoptin induced apoptosis with comparable efficiency in p53-/- and parental matched p53 wild-type HCT116 cells. p73 knockdown by siRNA in HCT116 cells significantly reduced sensitivity of the cells to apoptin-mediated killing, indicating the importance of p73 in apoptin cytotoxicity. Study of the p73 modulators demonstrated that the induction of apoptosis by apoptin was significantly higher in wild-type than in cells lacking p73 co-transcription factor, p300. However, knockdown of PML in H357 head and neck cancer cell line using shRNA had no effect on apoptin killing, suggesting that p300 but not PML may play a role in apoptin-induced cell death. -- Apoptin was found to bind and significantly increase TAp73[alpha] stability but importantly it had no effect on the level of the anti-apoptotic isoform [Delta]Np73[alpha].

Biochemical And Biophysical Aspects Of Apoptin A Tumor Specific Apoptosis Inducing Protein

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Author : Sirik Rutger Leliveld
language : en
Publisher:
Release Date : 2003

Biochemical And Biophysical Aspects Of Apoptin A Tumor Specific Apoptosis Inducing Protein written by Sirik Rutger Leliveld and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.

Apoptin

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Author : Rhyenne Misjenou Eline Zimmerman
language : en
Publisher:
Release Date : 2011

Apoptin written by Rhyenne Misjenou Eline Zimmerman and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.

Characterization Of The Interaction Between The Chicken Anaemia Virus Protein Apoptin And The Anaphase Promoting Complex

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Author : Russell Towers
language : en
Publisher:
Release Date : 2010

Characterization Of The Interaction Between The Chicken Anaemia Virus Protein Apoptin And The Anaphase Promoting Complex written by Russell Towers and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.

Gene Therapeutic Application Of The Chicken Anemia Virus Derived Protein Apoptin

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Author : Sharon Olijslagers
language : de
Publisher:
Release Date : 2002

Gene Therapeutic Application Of The Chicken Anemia Virus Derived Protein Apoptin written by Sharon Olijslagers and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with categories.

Biochemical And Biophysical Aspects Of Apoptin A Tumour Specific Apoptosis Inducing Protein

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Author : Sirik Rutger Leliveld
language : en
Publisher:
Release Date : 2003

Biochemical And Biophysical Aspects Of Apoptin A Tumour Specific Apoptosis Inducing Protein written by Sirik Rutger Leliveld and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.

Cancer Related Targets Sensed By Apoptin

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Author : Henrïette Leonore Lanz
language : en
Publisher:
Release Date : 2012

Cancer Related Targets Sensed By Apoptin written by Henrïette Leonore Lanz and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.

Apoptin And Its Derivatives As Molecular Clues Towards The Development Of Novel Tyrosine Kinase Inhibitors

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Author : Soumya Panigrahi
language : en
Publisher:
Release Date : 2008

Apoptin And Its Derivatives As Molecular Clues Towards The Development Of Novel Tyrosine Kinase Inhibitors written by Soumya Panigrahi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.

The non-receptor tyrosine kinase activity of fusion gene BCR-ABL derived oncoproteins is the key factor responsible for development and progress of Philadelphia positive (Ph+) chronic myeloid leukemia (CML). In the search for a superior and novel peptide-based inhibitor of Bcr-Abl, here I investigated a naturally occurring molecule, called apoptin. Apoptin is a 13.6 kDa protein derived from chicken anemia virus (CAV) and known to induce apoptosis in a wide range of transformed but not in primary cells. Apoptin is a protein without any reported structural and/or functional homolog and is an interesting candidate to initiate protein-protein interactions and subsequent downstream effects. Initially by an array-based analysis I found that apoptin interacts with the SH3 domain of Abl. By high stringency pull-down and co-immunoprecipitation assays the apoptin and Bcr-Abl interaction was further confirmed. Subsequently, a set of apoptin and Bcr-Abl deletion mutants were used to map this interaction precisely that mainly occurred between a proline rich domain of apoptin and the SH3 domain of Bcr-Abl. I further investigated the role of apoptin on Bcr-Abl. Apoptin was able to modify the phosphorylation of a series of targets (e.g. CrkL, STAT5, c-Myc) downstream of Bcr-Abl kinase. In addition, I used computational algorhythms for protein modeling to study the 3D structure of apoptin and it's docking with Bcr-Abl at the molecular level. In controlled studies using the 2-pheny-laminopyrimidine derived specific tyrosine kinase inhibitor Imatinib® I found that apoptin has comparable effects on CML cells, suggesting that the interacting segment of the apoptin molecule acts as an adaptor and negatively regulates the Bcr-Abl kinase by deactivating many cell proliferation and anti-apoptotic pathways in CML cells. Briefly, this work provides important insights towards the development of peptide based tyrosine kinase inhibitors as new anti-cancer agents.

Investigation Of The Apoptin Tumour Specific Kinase S

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Author : Daryl Cole
language : en
Publisher:
Release Date : 2013

Investigation Of The Apoptin Tumour Specific Kinase S written by Daryl Cole and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with Protein kinases categories.

The results indicate that PKG and PKC expression is potentially linked to Apoptin function in the cell lines tested. In addition, a newly discovered Human gyrovirus (HGyV) Apoptin was shown to have a similar cellular localisation to CAV Apoptin, and was also found to be toxic to transformed cells, though more indiscriminately than CAV Apoptin. In conclusion, the results presented here in this study propose a novel role for PKG and PKC in the tumour specific activation of Apoptin in normal and transformed cells. In the absence of PKG, transformed cells activate Apoptin through PKC leading to nuclear localisation and apoptosis. PKG expression in normal cells appears to block this process, resulting in cytoplasmic localisation of Apoptin and abrogation of Apoptin induced cell death. Additionally, the novel viral protein human gyrovirus Apoptin has been shown to behave in a similar manner to CAV Apoptin, providing a further tumour specific protein for future study. The information obtained during this study will therefore be important in the development of therapeutic strategies for not only determining sensitivity to Apoptin of certain tumours but also for the sensitisation of tumour cells to Apoptin.