Abstract
Par-4 functions as a tumor suppressor antagonizing the transforming capacity and the resistance of malignant cells towards apoptotic stimuli. After demonstrating that par-4 promotes apoptosis by activating signaling of the intrinsic pathway of apoptosis, we hypothesized that par-4 also impacts on key molecules of the extrinsic pathway without the requirement of a receptor/ligand interaction. Here, we provide first evidence, that expression of par-4 increases cleavage of caspase-8, truncation of Bid and its translocation to the mitochondria, resulting in an augmentation of cytochrome c and AIF efflux into the cytosol, effects par-4-positive cells are able to retain to a higher extent than par-4-negative cells upon inhibition of caspase-3 activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibiotics, Antineoplastic / pharmacology*
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins
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BH3 Interacting Domain Death Agonist Protein
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Carrier Proteins / metabolism
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Caspase 8
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Caspases / metabolism*
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Cytochromes c / metabolism*
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Doxorubicin / pharmacology*
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Gene Expression Regulation, Leukemic / drug effects
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Humans
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Mitochondria / metabolism*
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Protein Transport / drug effects
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Signal Transduction / drug effects
Substances
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Antibiotics, Antineoplastic
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Apoptosis Regulatory Proteins
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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prostate apoptosis response-4 protein
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Doxorubicin
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Cytochromes c
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CASP8 protein, human
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Caspase 8
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Caspases