LMO2 blocks the UBA6-USE1 interaction and downstream FAT10ylation by targeting the ubiquitin fold domain of UBA6

作者：Wu, Chao; Liu, Ye; Gu, Xiangxiang; Zhu, Tianhui; Yang, Shuang^*; Sun, Wei^*

来源：Biochemical and Biophysical Research Communications, 2016, 478(3): 1442-1448.

DOI：10.1016/j.bbrc.2016.08.143

• LMO2
• UBA6
• USE1
• FAT10ylation

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 Cterminal 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 FAT10-ylation 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.

• 出版日期2016-9-23
• 单位南开大学