A5069507613- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Toxin Mechanisms and Immunotoxins
- Cell death mechanisms and regulation
- Calcium signaling and nucleotide metabolism
- Integrated Circuits and Semiconductor Failure Analysis
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- Advanced Proteomics Techniques and Applications
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Electrostatic Discharge in Electronics
- Neuropeptides and Animal Physiology
- Biochemical and Molecular Research
- Mass Spectrometry Techniques and Applications
- RNA modifications and cancer
- Growth Hormone and Insulin-like Growth Factors
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Signaling Pathways in Disease
Université Laval
2015-2025
Centre hospitalier de l'Université Laval
2009-2024
Centre hospitalier universitaire de Québec
2003-2024
Quebec Research and Development Centre
2016-2024
University of California, San Diego
2024
University of Waterloo
2010-2023
Cancer Research Center
2020-2021
University of Alabama at Birmingham
2019
Sir Ganga Ram Hospital
2018
KLE Society Hospital
2018
Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that activation required for translocation apoptosis-inducing factor (AIF) from mitochondria to nucleus AIF necessary PARP-1-dependent death. N-methyl-N'-nitro-N-nitrosoguanidine, H2O2, N-methyl-d-aspartate induce death, which prevented PARP...
Poly(ADP-ribosyl)ation is a post-translational modification of proteins. During this process, molecules ADP-ribose are added successively on to acceptor proteins form branched polymers. This transient but very extensive in vivo, as polymer chains can reach more than 200 units protein acceptors. The existence the poly(ADP-ribose) was first reported nearly 40 years ago. Since then, importance synthesis has been established many cellular processes. However, clear and unified picture...
Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation. How PARP-1 activation leads AIF release not known. Here we identify PAR polymer as signal that induces of AIF. and translocation nucleus. glycohydrolase, which degrades polymer, prevents PARP-1-dependent release. Cells with reduced levels are resistant cytotoxicity. These results reveal an AIF-releasing plays...
Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various models cellular injury. Here, we identify (PAR) polymer, product PARP-1 activity, as previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, and degradation by glycohydrolase (PARG) or phosphodiesterase 1 prevents polymer-induced death. PARP-1-dependent, NMDA excitotoxicity cortical neurons reduced neutralizing antibodies overexpression PARG....
Poly(ADP-ribosyl)ation is a post-translational modification of proteins. During this process, molecules ADP-ribose are added successively on to acceptor proteins form branched polymers. This transient but very extensive in vivo, as polymer chains can reach more than 200 units protein acceptors. The existence the poly(ADP-ribose) was first reported nearly 40 years ago. Since then, importance synthesis has been established many cellular processes. However, clear and unified picture...
Genetic analyses of Caenorhabditis elegans has identified three genes that function in the regulation nematode cell death. Mammalian homologs two these genes, ced-9 and ced-3, have been comprise proteins belonging to Bcl-2 ICE families, respectively. To date, it is unclear where negative regulators, bcl-2, relative death effectors, ced-3 mammalian homologs, Here, molecular order pathway defined. Our results establish Bcl-xL upstream members ICE/CED-3 family cysteine proteases, Yama...
Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that rapidly activated by DNA strand breaks and signals the presence of lesions attaching ADP-ribose units to chromatin-associated proteins. The therapeutic applications PARP inhibitors in potentiating killing action ionizing radiation have been well documented are attracting increasing interest as cancer treatment. However, initial kinetics underlying recognition multiple PARP1 how inhibition potentiates activity DNA-damaging agents...
Although proteases related to the interleukin 1 beta-converting enzyme (ICE) are known be essential for apoptotic execution, number of enzymes involved, their substrate specificities, and specific roles in characteristic biochemical morphological changes apoptosis currently unknown. These questions were addressed using cloned recombinant ICE-related (IRPs) a cell-free model system (S/M extracts). First, we compared specificities two human IRPs, CPP32 Mch2 alpha. Both cleaved...
Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used cell-free system characterize that cleave nuclear lamins during apoptosis. Lamin cleavage apoptosis requires action second ICE-like enyzme, which exhibits kinetics and profile...
When rat pancreatic polynucleosomes were poly(ADP-ribosyl)ated with purified calf thymus poly(ADP-ribose) polymerase and examined by electron microscopy, a relaxation of their native zigzag structure was observed. At high ionic strengths control nucleosomes condensed into 250-A-thick fibers, but did not; they showed close resemblance to chromatin depleted histone H1. The relaxed state also confirmed sedimentation velocity analysis. Histone H1 found be the major acceptor poly(ADP-ribose)....
The prevention of apoptosis by Zn<sup>2+</sup> has generally been attributed to its inhibition an endonuclease acting in the late phase apoptosis. In this study we investigated effect on earlier event apoptotic process, proteolysis "death substrate" poly(ADP-ribose) polymerase (PARP). Pretreatment intact Molt4 leukemia cells with micromolar concentrations Zn<sup>2+</sup>caused PARP induced chemotherapeutic agent etoposide. Using a cell-free system consisting purified bovine as substrate and...
The abundant nuclear enzyme poly(ADP-ribose) polymerase (PARP) synthesizes in response to DNA strand breaks. During almost all forms of apoptosis, PARP is cleaved by caspases, suggesting the crucial role its inactivation. A few studies have also reported a stimulation during apoptosis. However, and cleavage this cell death process remains poorly understood. Here, we measured endogenous synthesis VP-16-induced apoptosis HL60 cells found that was caspases at time poly(ADP-ribosyl)ation. <i>In...
Poly(ADP-ribose) binds to apoptosis-inducing factor trigger its release from mitochondria and induce cell death.
Poly(ADP-ribose) (pADPr) is a polymer assembled from the enzymatic polymerization of ADP-ribosyl moiety NAD by poly(ADP-ribose) polymerases (PARPs). The dynamic turnover pADPr within cell essential for number cellular processes including progression through cycle, DNA repair and maintenance genomic integrity, apoptosis. In spite considerable advances in knowledge physiological conditions modulated poly(ADP-ribosyl)ation reactions, notwithstanding fact that can play role mediator wide...
PAR promotes α-synuclein toxicity How pathologic (α-syn) leads to neurodegeneration in Parkinson's disease (PD) remains poorly understood. Kam et al. studied the α-syn preformed fibril (α-syn PFF) model of sporadic PD (see Perspective by Brundin and Wyse). They found that α-syn–activated poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase–1 (PARP-1) inhibition PARP or knockout PARP-1 protected mice from pathology. The generation PFF–induced activation converted PFF a strain was 25-fold...