Human asparagine synthetase associates with the mitotic spindle

Biology Open

Vorasuk Shotelersuk¹  Chalongrat Noree²  Elena Monfort³ 

[1] Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;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;

关键词: Asparagine synthetase;    Mitotic spindle;    Mitosis;    Cell division;   

DOI  :  10.1242/bio.038307

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown