Abstract
Tumor necrosis factor apoptosis ligand (TRAIL) is a type II membrane-bound ligand displaying expression in a broad range of tissues and exhibiting a high grade of homology with the cytotoxic Fas ligand. Interest in TRAIL grew after evidence emerged, that induction of TRAIL-mediated signaling destroyed malignant cells while sparing normal cells. Employing the extrinsic pathway of apoptosis, TRAIL-stimulation is characterized by initial adaptor recruitment and the subsequent activation of caspases. Besides promoting apoptosis, stimulation of the TRAIL receptors may also activate survival signals via the transcription factor NF-κB. Moreover, evaluation of the physiological roles of TRAIL-mediated signaling pathways provides evidence for a regulatory function within the immune system. Thus a complex picture of TRAIL-mediated signaling evolves, underscoring the necessity to define its modes of action while assessing its therapeutic potential. This review outlines the current knowledge on the physiological role of TRAIL and discusses its therapeutic potential with particular focus on malignancies of the hematopoietic system.
Keywords: par-4, apoptosis, hematopoiesis, TRAIL
Current Medicinal Chemistry
Title: The Molecular Biology of TRAIL-Mediated Signaling and its PotentialTherapeutic Exploitation in Hematopoietic Malignancies
Volume: 13 Issue: 18
Author(s): Kai Uwe Chow, Paris S. Mitrou, Simone Boehrer, Daniel Nowak and Dieter Hoelzer
Affiliation:
Keywords: par-4, apoptosis, hematopoiesis, TRAIL
Abstract: Tumor necrosis factor apoptosis ligand (TRAIL) is a type II membrane-bound ligand displaying expression in a broad range of tissues and exhibiting a high grade of homology with the cytotoxic Fas ligand. Interest in TRAIL grew after evidence emerged, that induction of TRAIL-mediated signaling destroyed malignant cells while sparing normal cells. Employing the extrinsic pathway of apoptosis, TRAIL-stimulation is characterized by initial adaptor recruitment and the subsequent activation of caspases. Besides promoting apoptosis, stimulation of the TRAIL receptors may also activate survival signals via the transcription factor NF-κB. Moreover, evaluation of the physiological roles of TRAIL-mediated signaling pathways provides evidence for a regulatory function within the immune system. Thus a complex picture of TRAIL-mediated signaling evolves, underscoring the necessity to define its modes of action while assessing its therapeutic potential. This review outlines the current knowledge on the physiological role of TRAIL and discusses its therapeutic potential with particular focus on malignancies of the hematopoietic system.
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Cite this article as:
Uwe Chow Kai, Mitrou S. Paris, Boehrer Simone, Nowak Daniel and Hoelzer Dieter, The Molecular Biology of TRAIL-Mediated Signaling and its PotentialTherapeutic Exploitation in Hematopoietic Malignancies, Current Medicinal Chemistry 2006; 13 (18) . https://dx.doi.org/10.2174/092986706777935294
DOI https://dx.doi.org/10.2174/092986706777935294 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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