Oncotarget

Research Papers: Immunology:

This article has been corrected. Correction in: Oncotarget. 2018; 9:37343.

Inhibition of neddylation regulates dendritic cell functions via Deptor accumulation driven mTOR inactivation

Mengmeng Cheng, Shurong Hu, Zhengting Wang, Yaofei Pei, Rong Fan, Xiqiang Liu, Lei Wang, Jie Zhou, Sichang Zheng, Tianyu Zhang, Yun Lin, Maochen Zhang, Ran Tao and Jie Zhong _

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Oncotarget. 2016; 7:35643-35654. https://doi.org/10.18632/oncotarget.9543

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Abstract

Mengmeng Cheng1,*, Shurong Hu1,*, Zhengting Wang1, Yaofei Pei2, Rong Fan1, Xiqiang Liu2, Lei Wang1, Jie Zhou1, Sichang Zheng1, Tianyu Zhang1, Yun Lin1, Maochen Zhang1, Ran Tao3 and Jie Zhong1

1 Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

2 Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3 Department of Hepatobiliary-Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Jie Zhong, email:

Ran Tao, email:

Keywords: neddylation, dendritic cell, mTOR, Deptor, inflammatory bowel disease, Immunology and Microbiology Section, Immune response, Immunity

Received: October 27, 2015 Accepted: May 09, 2016 Published: May 21, 2016

Abstract

Neddylation, a newly identified post-translational modification, is significant for the activity and stability of target proteins. The exact role of neddylation in the pathogenesis of inflammatory bowel disease, specifically those mediated by dendritic cells (DCs), was still rarely reported. Here, we showed that inhibition of neddylation protected mice from mucosal inflammation. Targeting neddylation also inhibited DC maturation characterized by reduced cytokine production, down-regulated costimulatory molecules and suppressed capacity in allogeneic T cell stimulation. Additionally, inactivation of neddylation promotes caspase dependent apoptosis of DCs. These phenomena were attributed to the inactivation of mTOR, which was caused by Cullin-1 deneddylation induced Deptor accumulation. Together, our findings revealed that neddylation inhibition suppressed DC functions through mTOR signaling pathway and provided a potential therapeutic opportunity in inflammatory bowel diseases.


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