iProXProteomicsJingJing LiHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0006769000tide7@163.comCAS Key Laboratory of Nutrition, Metabolism and Food Safety Shanghai Institute of Nutrition and Health, University of Chinese Academy of SciencesiProXMetastasis is the main cause of colorectal cancer (CRC)-related death, and the 5-year relative survival rate for CRC patients with distant metastasis is only 14%. X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a zinc-rich protein belonging to the interferon (IFN)-induced gene family. Here, we report a metastasis-promoting role of XAF1 in CRC by acting as a novel adaptor of valosin-containing protein (VCP). XAF1 facilitates VCP-mediated deubiquitination of the E3 ligase RING finger protein 114 (RNF114), which promotes K48-linked ubiquitination and subsequent degradation of junction plakoglobin (JUP). The XAF1-VCP-RNF114-JUP axis is critical for the migration and metastasis of CRC cells. Moreover, we observe correlations between the protein levels of XAF1, RNF114, and JUP in clinical samples. Collectively, our findings reveal an oncogenic function of XAF1 in mCRC and suggest that the XAF1-VCP-RNF114-JUP axis is a potential therapeutic target for CRC treatment.XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.Xia Ji J, Ma Ning N, Shi Qian Q, Liu Qin-Cheng QC, Zhang Wei W, Cao Hui-Jun HJ, Wang Yi-Kang YK, Zheng Qian-Wen QW, Ni Qian-Zhi QZ, Xu Sheng S, Zhu Bing B, Qiu Xiao-Song XS, Ding Kai K, Huang Jing-Yi JY, Liang Xin X, Chen Yu Y, Xiang Yan-Jun YJ, Zhang Xi-Ran XR, Qiu Lin L, Chen Wei W, Xie Dong D, Wang Xiang X, Long Lingyun L, Li Jing-Jing JJfalseGel-based LC-MSMS, the interactome of RNF114 in 293T cellsWe utilized mass spectrometry to analyze the interactome of RNF114 in 293T cells.Mon Aug 07 00:00:00 BST 2023PXD044440960638095639