Noree Chalongrat, Monfort Elena, Shotelersuk Vorasuk
Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon 4 Road, Salaya, Phuttamonthon, Nakhon Pathom 73170, Thailand
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive (MC 0347), La Jolla, CA 92093-0347, USA.
Biol Open. 2018 Dec 14;7(12):bio038307. doi: 10.1242/bio.038307.
Cancer cells are characterized by extensive reprogramming of metabolic pathways in order to promote cell division and survival. However, the growth promotion effects of metabolic reprogramming can be due to moonlighting functions of metabolic enzymes as well as the redirection of flux through particular pathways. To identify metabolic enzymes that might have potential moonlighting functions in oncogenesis, we have examined recent screens of the yeast GFP strain collection for metabolic enzymes that have been implicated in cancer metabolism with an unusual subcellular localization. Asparagine synthetase forms filaments in yeast in response to nutrient limitation and is part of a pathway that is a chemotherapy target in acute lymphoblastic leukemia. Interestingly, while yeast asparagine synthetase forms cytoplasmic filaments in response to nutrient stress, human asparagine synthetase is associated with the centrosomes and mitotic spindles. This localization is disrupted by both nocodazole and asparaginase treatments. This failure to localize occurs even though asparagine synthetase is highly upregulated in response to asparaginase treatment. Together, these results argue that human asparagine synthetase undergoes regulated recruitment to the mitotic spindles and that it may have acquired a second role in mitosis similar to other metabolic enzymes that contribute to metabolic reprogramming in cancer cells.
癌细胞的特征是代谢途径广泛重编程，以促进细胞分裂和存活。然而，代谢重编程的促生长作用可能归因于代谢酶的兼职功能以及特定途径中通量的重新定向。为了鉴定可能在肿瘤发生中具有潜在兼职功能的代谢酶，我们检查了最近对酵母绿色荧光蛋白（GFP）菌株库的筛选，寻找那些与癌症代谢相关且具有异常亚细胞定位的代谢酶。天冬酰胺合成酶在酵母中响应营养限制形成细丝，并且是急性淋巴细胞白血病化疗靶点所在途径的一部分。有趣的是，虽然酵母天冬酰胺合成酶在响应营养应激时形成细胞质细丝，但人类天冬酰胺合成酶与中心体和有丝分裂纺锤体相关。这种定位会被诺考达唑和天冬酰胺酶处理破坏。即使天冬酰胺合成酶在响应天冬酰胺酶处理时高度上调，这种定位失败仍会发生。这些结果共同表明，人类天冬酰胺合成酶会被调控募集到有丝分裂纺锤体，并且它可能在有丝分裂中获得了第二个作用，类似于其他有助于癌细胞代谢重编程的代谢酶。
