TFEB 核易位在银纳米颗粒诱导的细胞保护性自噬中的关键作用。
Key Role of TFEB Nucleus Translocation for Silver Nanoparticle-Induced Cytoprotective Autophagy.
机构信息
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, 230027, China.
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, China.
出版信息
Small. 2018 Mar;14(13):e1703711. doi: 10.1002/smll.201703711. Epub 2018 Feb 19.
Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a well-established mechanism involving dephosphorylation of TFEB at serine-142 and serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus translocation precedes autophagy induced by Ag NPs and leads to enhanced expression of autophagy-essential genes. Knocking down the expression of TFEB attenuates the autophagy induction is demonstrated, and in the meantime, enhanced cell killing in HeLa cells treats with Ag NPs, indicating that TFEB is the key mediator for Ag NPs-induced cytoprotective autophagy. The results pinpoint TFEB as a potential target for developing more effective Ag NPs-based cancer therapeutics.
转录因子 EB（TFEB）是自噬和溶酶体生物发生的主要调节因子。本文显示，银纳米粒子（Ag NPs）诱导的细胞保护性自噬需要 TFEB。Ag NPs 通过一种成熟的机制诱导 TFEB 核转位，该机制涉及 TFEB 在丝氨酸-142 和丝氨酸-211 上的去磷酸化，但不依赖于 mTORC1 和 ERK1/2 途径。TFEB 的核转位先于 Ag NPs 诱导的自噬，并导致自噬必需基因的表达增强。敲低 TFEB 的表达可减弱自噬的诱导，同时增强用 Ag NPs 处理的 HeLa 细胞的细胞杀伤，表明 TFEB 是 Ag NPs 诱导的细胞保护性自噬的关键介质。这些结果表明 TFEB 是开发更有效的基于 Ag NPs 的癌症治疗方法的潜在靶点。
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