title: Lysine residues 639 and 673 of mouse Ncoa3 are ubiquitination sites for the regulation of its stability.
abstract: 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 arginine, 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 ubiquitination 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.
authors.affiliation: State key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Mou
authors.affiliation: State key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Weiyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin 300071, China lingyichen@nankai.edu.cn.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D056921:Nuclear Receptor Coactivator 3 / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D060888:Real-Time Polymerase Chain Reaction; D054875:Ubiquitination
chemical_list: C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3; D008239:Lysine
keywords: Ncoa3; proteasomal degradation; protein stability; ubiquitination