title: LMO2 blocks the UBA6-USE1 interaction and downstream FAT10ylation by targeting the ubiquitin fold domain of UBA6.
abstract: In eukaryotic cells, the post-translational modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is the most common trigger for protein degradation and is involved in the regulation of a wide range of biological processes. FAT10 (HLA-F-adjacent transcript 10), which belongs to the UBL family, is activated specifically through the UBA6-USE1 cascade and targets substrates covalently for 26S proteasomal degradation. LMO2 is a well-recognized transcriptional regulator in hematopoietic and endothelial systems; however, it is predominantly located in the cytoplasm of epithelium-derived cells. The current study revealed that LMO2 protein interacted with the E1 ubiquitin-activating enzyme UBA6 at the C-terminal ubiquitin fold domain (UFD), which mediates the recognition and recruitment of the E2-conjugating enzyme USE1. Functionally, the LMO2-UBA6 interaction disturbed the interaction between UBA6 and USE1 and led to the decline of the overall cellular FAT10ylation level as well as the FAT10ylation and degradation of a known FAT10 substrate p62. Taken together, this study revealed a novel function of LMO2 involving in the regulatory hierarchy of UBA6-USE1-FAT10ylation pathway by targeting the E1 enzyme UBA6.
authors: Laboratory of Molecular Genetics in School of Medicine, Nankai University, Tianjin, China.
authors: Chao
authors: C
authors: Wu
authors: Laboratory of Molecular Genetics in School of Medicine, Nankai University, Tianjin, China.
authors: Ye
authors: Y
authors: Liu
authors: Laboratory of Molecular Genetics in School of Medicine, Nankai University, Tianjin, China.
authors: Xiangxiang
authors: X
authors: Gu
authors: Laboratory of Molecular Genetics in School of Medicine, Nankai University, Tianjin, China.
authors: Tianhui
authors: T
authors: Zhu
authors: Laboratory of Molecular Genetics in School of Medicine, Nankai University, Tianjin, China. Electronic address: yangshuang@nankai.edu.cn.
authors: Shuang
authors: S
authors: Yang
authors: Laboratory of Molecular Genetics in School of Medicine, Nankai University, Tianjin, China. Electronic address: sunweibio@nankai.edu.cn.
authors: Wei
authors: W
authors: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050600:SNARE Proteins; D025801:Ubiquitin / Q000737:chemistry*; D044764:Ubiquitin-Activating Enzymes / Q000737:chemistry* / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins; D050600:SNARE Proteins; C521757:UBA6 protein, human; C109184:UBD protein, human; D025801:Ubiquitin; D014452:Ubiquitins; C521756:Use1 protein, human; D033921:Vesicular Transport Proteins; D044764:Ubiquitin-Activating Enzymes
keywords: FAT10ylation; LMO2; UBA6; USE1