Oncotarget

Research Papers:

RNF4-mediated SUMOylation is essential for NDRG2 suppression of lung adenocarcinoma

Jicheng Tantai, Xufeng Pan and Dingzhong Hu _

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Oncotarget. 2016; 7:26837-26843. https://doi.org/10.18632/oncotarget.8663

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Abstract

Jicheng Tantai1, Xufeng Pan1, Dingzhong Hu1

1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

Correspondence to:

Dingzhong Hu, e-mail: [email protected]

Keywords: NDRG2, RNF4, SUMOylation, tumorigenesis, STUbL

Received: October 27, 2015     Accepted: March 06, 2016     Published: April 09, 2016

ABSTRACT

N-Myc downstream-regulated gene 2 (NDRG2) protein is a tumor suppressor that inhibits cancer growth, metastasis and invasion. The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin through its selective recognition and ubiquitination of SUMO-modified proteins. We evaluated NDRG2 SUMOylation in lung adenocarcinoma cells and its underlying molecular mechanism. The results showed that NDRG2 is covalently modified by SUMO1 at K333, which suppressed anchorage independent adenocarcinoma cell proliferation and tumor growth. In human lung adenocarcinomas cells, RNF4 targeted NDRG2 to proteasomal degradation by stimulating its SUMOylation. Endogenous RNF4 expression was increased in human lung adenocarcinomas cells, and there was a concomitant upregulation of SUMO. These findings indicate that SUMOylation of NDRG2 is necessary for its tumor suppressor function in lung adenocarcinoma and that RNF4 increases the efficiency of this process.


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