Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, China; State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, China; State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China.
Cancer Lett. 2018 May 1;421:82-93. doi: 10.1016/j.canlet.2018.02.021. Epub 2018 Feb 17.
Peroxisome houses a large number of enzymes involved in lipid and phytochemical oxidation as well as synthesis of bile acid and other specialized lipids. Peroxisome resident enzymes are imported into the organelle via a conserved cargo transport system composed of many peroxins, protein factors essential for the biogenesis of peroxisome. Among the peroxins, PEX5 plays a transporter role, and PEX2, 10, and 12 are thought to form a complex that functions as an E3 ubiquitin ligase to help recycle PEX5 in an ubiquitin modification-dependent process. Previous studies have demonstrated the importance of peroxins in postnatal development especially the development of nerve systems. These studies also show that peroxins or the function of peroxisomes is dispensable for cellular viability. In contrast, however, we report here that PEX2 and other peroxins are essential for the viability of liver cancer cells, probably through altering metabolism and signaling pathways. Our results suggest that peroxins may be potential targets of therapeutics against liver cancer.
过氧化物酶体中含有大量参与脂质和植物化学物质氧化以及胆汁酸和其他特殊脂质合成的酶。过氧化物酶体驻留酶通过由许多过氧化物酶组成的保守货物运输系统被导入细胞器，过氧化物酶是过氧化物酶体生物发生所必需的蛋白因子。在过氧化物酶中，PEX5 起转运体作用，PEX2、10 和 12 被认为形成一个复合物，作为 E3 泛素连接酶，以帮助在依赖泛素修饰的过程中回收 PEX5。先前的研究表明过氧化物酶在出生后发育中尤其是神经系统发育中的重要性。这些研究还表明，过氧化物酶或过氧化物酶体的功能对于细胞活力不是必需的。然而，与这些研究结果相反，我们在这里报道 PEX2 和其他过氧化物酶对于肝癌细胞的活力是必需的，可能是通过改变代谢和信号通路。我们的结果表明，过氧化物酶可能是肝癌治疗的潜在靶点。
