摘要
脯氨酸脱氢酶/脯氨酸氧化酶(PRODH / POX)是一种催化脯氨酸第一步降解的酶,过程中产生ROS和ATP。POX广泛分布于生物体中,并负责一些调节过程,如氧化还原稳态,渗透调节,细胞信号和氧化应激。最近数据表明,POX在肿瘤发生和肿瘤生长中起着重要的作用。POX可通过内在和外在的方式诱导细胞凋亡。由于ROS的产生,POX可诱导caspase-9活性,其可介导线粒体凋亡(内源性凋亡途径)。POX也能刺激TRAIL(肿瘤坏死因子相关凋亡诱导配体)和DR5(死亡受体5)的表达,导致procaspase-8裂解和外源性凋亡。然而,这种抑癌基因在一定环境条件下可作为一种促生存因子,但遗传毒性,炎症和代谢应激可能使POX从抑制肿瘤生长转为促进肿瘤生长。本文将讨论可以调节切换POX模式的潜在机制。
关键词: 细胞凋亡,癌,脯氨酸脱氢酶(PRODH),脯氨酸氧化酶(POX)。
图形摘要
Current Drug Targets
Title:Proline Oxidase (POX) as A Target for Cancer Therapy
Volume: 16 Issue: 13
Author(s): Joanna Kononczuk, Urszula Czyzewska, Joanna Moczydlowska, Arkadiusz Surażyński, Jerzy Palka and Wojciech Miltyk
Affiliation:
关键词: 细胞凋亡,癌,脯氨酸脱氢酶(PRODH),脯氨酸氧化酶(POX)。
摘要: Proline dehydrogenase/proline oxidase (PRODH/POX) is an enzyme catalyzing the first step of proline degradation, during which ROS and/or ATP is generated. POX is widely distributed in living organisms and is responsible for a number of regulatory processes such as redox homeostasis, osmotic adaptation, cell signaling and oxidative stress. Recent data provided evidence that POX plays an important role in carcinogenesis and tumor growth. POX may induce apoptosis in both intrinsic and extrinsic way. Due to ROS generation, POX may induce caspase-9 activity, which mediates mitochondrial apoptosis (intrinsic apoptosis pathway). POX can also stimulate TRAIL (tumor necrosis factorrelated apoptosis inducing ligand) and DR5 (death receptor 5) expression, resulting in cleavage of procaspase-8 and thus extrinsic apoptotic pathway. However, this tumor suppressor in certain environmental conditions may act as a prosurvival factor. Genotoxic, inflammatory and metabolic stress may switch POX from tumor growth inhibiting to tumor growth supporting factor. The potential mechanisms which may regulate switching of POX mode are discussed in this review.
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Joanna Kononczuk, Urszula Czyzewska, Joanna Moczydlowska, Arkadiusz Surażyński, Jerzy Palka and Wojciech Miltyk , Proline Oxidase (POX) as A Target for Cancer Therapy, Current Drug Targets 2015; 16 (13) . https://dx.doi.org/10.2174/138945011613151031150637
DOI https://dx.doi.org/10.2174/138945011613151031150637 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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