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Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE
A novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder.
Mammalian caspases: structure, activation, substrates, and functions during apoptosis.
This work has shown that apoptotic cell death is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli, and that proteases play critical roles in initiation and execution of this process.
PARP inhibition: PARP1 and beyond
- M. Rouleau, Anand G. Patel, M. Hendzel, S. Kaufmann, G. Poirier
- BiologyNature Reviews. Cancer
- 1 April 2010
What is known about the structures and functions of the family ofPARP enzymes are reviewed, and a series of questions that should be addressed are outlined to guide the rational development of PARP inhibitors as anticancer agents.
Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis.
- S. Kaufmann, S. Desnoyers, Y. Ottaviano, N. Davidson, G. Poirier
- Biology, ChemistryCancer Research
- 1 September 1993
The results suggest that proteolytic cleavage of pADPRp, in addition to being an early marker of chemotherapy-induced apoptosis, might reflect more widespread proteolysis that is a critical biochemical event early during the process of physiological cell death.
Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.
Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells
- Anand G. Patel, J. Sarkaria, S. Kaufmann
- BiologyProceedings of the National Academy of Sciences
- 7 February 2011
It is shown that PARP inhibitor treatment induces phosphorylation of DNA-dependent protein kinase substrates and stimulates error-prone nonhomologous end joining (NHEJ) selectively in HR-deficient cells, and it is indicated that deregulated NHEJ plays a major role in generating the genomic instability and cytotoxicity in HRs treated with PARP inhibitors.
Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c.
- M. E. Guicciardi, J. Deussing, G. Gores
- Biology, ChemistryJournal of Clinical Investigation
- 1 November 2000
Caspase-mediated release of cat B from lysosomes enhances mitochondrial release of cytochrome c and subsequent caspase activation in TNF-alpha-treated hepatocytes.
Induction of apoptosis by cancer chemotherapy.
The two prototypic death pathways are described, current understanding of the role of the two pathways in chemotherapy-induced apoptosis is summarized, and the implications of these studies for mechanisms of resistance to chemotherapeutic agents are discussed.
Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma.
It is demonstrated that agents that selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit and single-agent temsirolimus has substantial antitumor activity in relapsed MCL.
Loss of HSulf-1 Up-regulates Heparin-binding Growth Factor Signaling in Cancer*
Observations provide evidence that HSulf-1 modulates signaling by heparin-binding growth factors, and HS sulfur-1 down-regulation represents a novel mechanism by which cancer cells can enhance growth factor signaling.