title: RNF4-mediated SUMOylation is essential for NDRG2 suppression of lung adenocarcinoma.
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.
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Tantai
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Dingzhong
authors.initials: D
authors.lastname: Hu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C466228:NDRG2 protein, human; D009687:Nuclear Proteins; C114070:RNF4 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: NDRG2; RNF4; STUbL; SUMOylation; tumorigenesis