Division of Biological Sciences, Department of Life Systems, Research Center for Women's Disease, Sookmyung Women's University, Seoul, Korea.
New Drug Development Center, Osong Medical Innovation Foundation, Osong, Korea.
EMBO Rep. 2018 May;19(5). doi: 10.15252/embr.201745144. Epub 2018 Feb 28.
In most mammalian cells, the primary cilium is a microtubule-enriched protrusion of the plasma membrane and acts as a key coordinator of signaling pathways during development and tissue homeostasis. The primary cilium is generated from the basal body, and cancerous inhibitor of protein phosphatase 2A (CIP2A), the overexpression of which stabilizes c-MYC to support the malignant growth of tumor cells, is localized in the centrosome. Here, we show that CIP2A overexpression induces primary cilia disassembly through the activation of Aurora A kinase, and CIP2A depletion increases ciliated cells and cilia length in retinal pigment epithelium (RPE1) cells. CIP2A depletion also shifts metabolism toward the glycolytic pathway by altering the expression of metabolic genes related to glycolysis. However, glycolytic activation in CIP2A-depleted cells does not depend on cilia assembly, even though enhanced cilia assembly alone activates glycolytic metabolism. Collectively, these data suggest that CIP2A promotes primary cilia disassembly and that CIP2A depletion induces metabolic reprogramming independent of primary cilia.
在大多数哺乳动物细胞中，初级纤毛是质膜的富含微管的突起，在发育和组织稳态过程中充当信号通路的关键协调器。初级纤毛由基体产生，癌性蛋白磷酸酶 2A 抑制剂（CIP2A）的过表达稳定 c-MYC 以支持肿瘤细胞的恶性生长，定位于中心体。在这里，我们表明 CIP2A 过表达通过激活 Aurora A 激酶诱导初级纤毛解体，并且 CIP2A 耗竭增加视网膜色素上皮 (RPE1) 细胞中的纤毛细胞和纤毛长度。CIP2A 耗竭还通过改变与糖酵解相关的代谢基因的表达将代谢转向糖酵解途径。然而，即使增强的纤毛组装本身激活糖酵解代谢，CIP2A 耗竭细胞中的糖酵解激活也不依赖于纤毛组装。总的来说，这些数据表明 CIP2A 促进初级纤毛解体，并且 CIP2A 耗竭诱导独立于初级纤毛的代谢重编程。
