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Apoptotic signalling in virally infected and normal cells.
- Title
- Apoptotic signalling in virally infected and normal cells.
- Funding
- ARC | Future Fellowships
- Contract (GA) number
- FT0991464
- Start Date
- 2009/01/01
- End Date
- 2013/12/31
- Open Access mandate
- no
- Organizations
- -
- More information
- http://purl.org/au-research/grants/arc/FT0991464
-
Data on the DNA damaging and mutagenic potential of the BH3-mimetics ABT-263/Navitoclax and TW-37
Green, Maja M.; Shekhar, Tanmay M.; Hawkins, Christine J. (2016)
Projects: ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464)Unfortunately, the mutagenic activities of chemotherapy and radiotherapy can provoke development of therapy-induced malignancies in cancer survivors. Non-mutagenic anti-cancer therapies may be less likely to trigger subsequent malignant neoplasms. Here we present data regarding the DNA damaging and mutagenic potential of two drugs that antagonize proteins within the Bcl-2 family: ABT-263/Navitoclax and TW-37. Our data reveal that concentrations of these agents that stimulated Bax/Bak-dependen...IAP antagonists sensitize murine osteosarcoma cells to killing by TNF?
Shekhar, Tanmay M.; Miles, Mark A.; Gupte, Ankita; Taylor, Scott; Tascone, Brianna; Walkley, Carl R.; Hawkins, Christine J. (2016)
Projects: ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464)Outcomes for patients diagnosed with the bone cancer osteosarcoma have not improved significantly in the last four decades. Only around 60% of patients and about a quarter of those with metastatic disease survive for more than five years. Although DNA-damaging chemotherapy drugs can be effective, they can provoke serious or fatal adverse effects including cardiotoxicity and therapy-related cancers. Better and safer treatments are therefore needed. We investigated the anti-osteosarcoma activit...Analysis of the minimal specificity of caspase-2 and identification of Ac-VDTTD-AFC as a caspase-2-selective peptide substrate
Kitevska, Tanja; Roberts, Sarah J.; Pantaki-Eimany, Delara; Boyd, Sarah E.; Scott, Fiona L.; Hawkins, Christine J. (2014)
Projects: ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464)Caspase-2 is an evolutionarily conserved but enigmatic protease whose biological role remains poorly understood. To date, research into the functions of caspase-2 has been hampered by an absence of reagents that can distinguish its activity from that of the downstream apoptotic caspase, caspase-3. Identification of protein substrates of caspase-2 that are efficiently cleaved within cells may also provide clues to the role of this protease. We used a yeast-based transcriptional reporter system...TRAIL treatment provokes mutations in surviving cells
Lovric, M M; Hawkins, C J (2010)
Projects: ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464), NHMRC | Analysis of apoptotic pathways to develop better therapies for unresponsive cancers. (541930)Chemotherapy and radiotherapy commonly damage DNA and trigger p53-dependent apoptosis through intrinsic apoptotic pathways. Two unfortunate consequences of this mechanism are resistance due to blockade of p53 or intrinsic apoptosis pathways, and mutagenesis of non-malignant surviving cells which can impair cellular function or provoke second malignancies. Death ligand-based drugs, such as tumor necrosis factor-related apoptosis inducing ligand (TRAIL), stimulate extrinsic apoptotic signaling,...Functional and biochemical characterization of the baculovirus caspase inhibitor MaviP35
Brand, I L; Green, M M; Civciristov, S; Pantaki-Eimany, D; George, C; Gort, T R; Huang, N; Clem, R J; Hawkins, C J (2011)
Projects: EC | PREPARE (602525), NHMRC | Viral caspase inhibitors (602525), ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464)Many viruses express proteins which prevent the host cell death that their infection would otherwise provoke. Some insect viruses suppress host apoptosis through the expression of caspase inhibitors belonging to the P35 superfamily. Although a number of P35 relatives have been identified, Autographa californica (Ac) P35 and Spodoptera littoralis (Spli) P49 have been the most extensively characterized. AcP35 was found to inhibit caspases via a suicide substrate mechanism: the caspase cleaves A...Yeast techniques for modeling drugs targeting Bcl-2 and caspase family members
Beaumont, T E; Shekhar, T M; Kaur, L; Pantaki-Eimany, D; Kvansakul, M; Hawkins, C J (2013)
Projects: ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464), NHMRC | Targeting viral anti-apoptotic proteins for therapy (637372), NHMRC | Viral caspase inhibitors (602525)Development of drugs targeting Bcl-2 relatives and caspases, for treating diseases including cancer and inflammatory disorders, often involves measuring interactions with recombinant target molecules, and/or monitoring cancer cell killing in vitro. Here, we present yeast-based methods for evaluating drug-mediated inhibition of Bcl-2 relatives or caspases. Active Bax and caspases kill Saccharomyces cerevisiae, and pro-survival Bcl-2 proteins can inhibit Bax-induced yeast death. By measuring th...Caspase inhibitors of the P35 family are more active when purified from yeast than bacteria.
Ingo L Brand; Srgjan Civciristov; Nicole L Taylor; Gert H Talbo; Delara Pantaki-Eimany; Vita Levina; Rollie J Clem; Matthew A Perugini; Marc Kvansakul; Christine J Hawkins
Projects: NHMRC | Viral caspase inhibitors (602525), NHMRC | Targeting viral anti-apoptotic proteins for therapy (637372), ARC | Molecular evolution of a model oligomeric enzyme from bacterial extremophiles (FT0991245), ARC | Apoptotic signalling in virally infected and normal cells. (FT0991464)Many insect viruses express caspase inhibitors of the P35 superfamily, which prevent defensive host apoptosis to enable viral propagation. The prototypical P35 family member, AcP35 from Autographa californica M nucleopolyhedrovirus, has been extensively studied. Bacterially purified AcP35 has been previously shown to inhibit caspases from insect, mammalian and nematode species. This inhibition occurs via a pseudosubstrate mechanism involving caspase-mediated cleavage of a “reactive site loop”... -
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Scientific Results
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