Par-4: a common facilitator/enhancer of extrinsic and intrinsic pathways of apoptosis.
Par-4 overexpression has been shown by Boehrer et al. to augment the apoptotic death of Jurkat T cells induced by TNF related Apoptosis Inducing Ligand (TRAIL). Previously, the same authors have demonstrated a parallel augmentation of chemotherapeutic drug-induced apoptosis in the same cell line overexpressing Par-4. Through these and other studies, Par-4 appears to emerge as a general intracellular facilitator of both extrinsic and intrinsic pathways of apoptosis. The ability of Par-4 to modulate relevant inhibitors of apoptosis and to facilitate activation of alternative initiator or executioner caspases in contingent situations may support its role as a common facilitator/enhancer of apoptotic cell death. Further understanding of Par-4 biology will have significant clinical implications especially in overcoming drug resistance phenomenon in cancer.
Mundle
Suneel D
SD
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C101296:prostate apoptosis response-4 protein; D020169:Caspases