Key Role of TFEB Nucleus Translocation for Silver Nanoparticle-Induced Cytoprotective Autophagy

Jun Lin; Yiming Liu; Hao Wu; Zhihai Huang; Jingfan Ma; Chang Guo; Feng Gao; Peipei Jin; Pengfei Wei; Yunjiao Zhang; Liu Liu; Rui Zhang; Longxin Qiu; Ning Gu; Longping Wen

doi:10.1002/smll.201703711

Key Role of TFEB Nucleus Translocation for Silver Nanoparticle-Induced Cytoprotective Autophagy

Small. 2018 Mar;14(13):e1703711. doi: 10.1002/smll.201703711. Epub 2018 Feb 19.

Authors

Jun Lin¹, Yiming Liu¹, Hao Wu², Zhihai Huang², Jingfan Ma³, Chang Guo³, Feng Gao¹, Peipei Jin¹, Pengfei Wei¹, Yunjiao Zhang¹, Liu Liu¹, Rui Zhang¹, Longxin Qiu³, Ning Gu², Longping Wen¹

Affiliations

¹ 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.
² State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, China.
³ Department of Biological Science and Technology, School of Life Sciences, Longyan University, Longyan, Fujian, 364012, China.

PMID: 29457340
DOI: 10.1002/smll.201703711

Abstract

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.

Keywords: TFEB dephosphorylation; autophagy; silver nanoparticles (Ag NPs); transcription factor EB (TFEB); tumor therapies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / drug effects*
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
Cell Nucleus / metabolism*
HeLa Cells
Humans
Metal Nanoparticles / chemistry*
Protein Transport / drug effects
Real-Time Polymerase Chain Reaction
Silver / chemistry*
Silver / pharmacology*

Substances

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
TFEB protein, human
Silver