PMID- 32736675 OWN - NLM STAT- MEDLINE DCOM- 20210222 LR - 20211204 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 529 IP - 3 DP - 2020 Aug 27 TI - NCOA5 is a master regulator of amino acid-induced mTOR activation and beta-casein synthesis in bovine mammary epithelial cells. PG - 569-574 LID - S0006-291X(20)31131-1 [pii] LID - 10.1016/j.bbrc.2020.05.193 [doi] AB - The nuclear receptor co-activator 5 (NCOA5) is known as a co-activator or co-repressor that influences gene expression and cellular physiology, but its roles and detailed molecular mechanism is still largely unknown. In this study, we explored the role and molecular mechanism of NCOA5 in amino acid-induced activation of the mechanistic target of rapamycin (mTOR) and milk protein synthesis in bovine mammary epithelial cells (BMECs). Methionine (Met) and leucine (Leu) significantly up-regulated the expression of NCOA5. NCOA5 overexpression increased mTOR phosphorylation and beta-casein synthesis, whereas its knockdown exhibited the opposite effects. Furthermore, inhibition of phosphatidylinositol 3-kinase (PI3K) completely abolished the stimulatory effects of Met and Leu on NCOA5 expression. ChIP-qPCR analysis detected that NCOA5 bound to the mTOR promoter, and this interaction was enhanced by the stimulation of Met and Leu. These above data reveal that NCOA5 is a key regulator of amino acid-induced PI3K-mediated mTOR activation and beta-casein synthesis in BMECs. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Yuan, Xiaohan AU - Yuan X AD - The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China. FAU - Zhang, Li AU - Zhang L AD - The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China. FAU - Cui, Yingjun AU - Cui Y AD - The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China. FAU - Yu, Yanbo AU - Yu Y AD - The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China. FAU - Gao, Xuejun AU - Gao X AD - School of Animal Science, Yangtze University, Jingzhou, China. FAU - Ao, Jinxia AU - Ao J AD - The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China. Electronic address: ajx050723@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200715 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Amino Acids) RN - 0 (Caseins) RN - 0 (Nuclear Receptor Coactivators) RN - AE28F7PNPL (Methionine) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - GMW67QNF9C (Leucine) SB - IM MH - Amino Acids/*pharmacology MH - Animals MH - Caseins/*metabolism MH - Cattle MH - Cells, Cultured MH - Enzyme Activation/drug effects MH - Epithelial Cells/*drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - Leucine/pharmacology MH - Mammary Glands, Animal/cytology/metabolism MH - Methionine/pharmacology MH - Nuclear Receptor Coactivators/genetics/*metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/genetics/*metabolism OTO - NOTNLM OT - Amino acid OT - Bovine mammary epithelial cells OT - NCOA5 OT - mTOR OT - beta-casein COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/08/02 06:00 MHDA- 2021/02/23 06:00 CRDT- 2020/08/02 06:00 PHST- 2020/05/12 00:00 [received] PHST- 2020/05/25 00:00 [accepted] PHST- 2020/08/02 06:00 [entrez] PHST- 2020/08/02 06:00 [pubmed] PHST- 2021/02/23 06:00 [medline] AID - S0006-291X(20)31131-1 [pii] AID - 10.1016/j.bbrc.2020.05.193 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2020 Aug 27;529(3):569-574. doi: 10.1016/j.bbrc.2020.05.193. Epub 2020 Jul 15.