Lysine residues 639 and 673 of mouse Ncoa3 are ubiquitination sites for the regulation of its stability

• Published in: Acta biochimica et biophysica Sinica Vol. 46; no. 12; pp. 1066 - 1071
• Main Authors: Mou, Chunlin, Zhang, Yanqin, Zhang, Weiyu, Ding, Yu, Chen, Lingyi
• Format: Journal Article
• Language: English
• Published: China 01.12.2014
• Subjects: Animals; HEK293 Cells; Humans; Lysine - metabolism; Mice; Nuclear Receptor Coactivator 3 - chemistry; Nuclear Receptor Coactivator 3 - metabolism; Protein Stability; Real-Time Polymerase Chain Reaction; Ubiquitination; 氨基酸残基; 泛素化; 生物过程; 稳定性; 蛋白表达; 调控; 赖氨酸; 鼠标; Ncoa3; ubiquitination; proteasomal degradation; protein stability
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmu096

Ncoa3 is a transcriptional coactivator involved in a wide range of biological processes. Regulation of Ncoa3 protein stability is important to control its activity precisely. Here, we found that deleting amino acid residues 614-740 of Ncoa3 enhances the protein expression level. Replacing two lysine residues, K639 and K673, within this region by argin- ine, increases the stability of the luciferase fusion protein as well as Ncoa3 protein. When these two lysine residues are mutated to arginine, the overall ubiquitination level of Ncoa3 decreases, indicating that lysine 639 and 673 are its ubiquiti- nation sites. Taken together, we identified two ubiquitination sites at lysine 639 and 673 of Ncoa3. Ubiquitination of these two lysine residues leads to proteasomal degradation of Ncoa3.