Regulation of transcription by AMP-activated protein kinase - Phosphorylation of p300 blocks its interaction with nuclear receptors

作     者：Yang, WB Hong, YH Shen, XQ Frankowski, C Camp, HS Leff, T 

作者机构：Pfizer Global Res & Dev Dept Mol Sci Ann Arbor MI 48105 USA Univ Michigan Sch Med Dept Biol Chem Ann Arbor MI 48109 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2001年第276卷第42期

页      面：38341-38344页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：Cell Nucleus Multienzyme Complexes Nuclear Proteins Protein-Serine-Threonine Kinases 细胞核 多酶复合物 核蛋白质类 蛋白质丝氨酸苏氨酸激酶 反式作用因子 转录 遗传 enzyme complexes Nuclear Proteins AMP-Activated Protein Kinases Nuclear receptors Energy Metabolism Genetic Transcription Protein-Serine-Threonine Kinases Transcription Coactivator Retinoid X Receptors 

摘      要：AMP-activated protein kinase (AMP-kinase) modulates many metabolic processes in response to fluctuations in cellular energy status. Although most of its known targets are metabolic enzymes, it has been proposed that AMP-kinase might also regulate gene expression. Here we demonstrate that the transcriptional coactivator p300 is a substrate of AMP-kinase. Phosphorylation of p300 at serine 89 by AMP-kinase dramatically reduced its interaction, in vitro and in vivo, with the nuclear receptors peroxisome proliferator-activated receptor gamma, thyroid receptor, retinoic acid receptor, and retinoid X receptor, but did not affect its interaction with the non-nuclear receptor transcription factors Ela, p53, or GATA4. These findings indicate that the AMP-kinase signaling pathway selectively modulates a subset of p300 activities and represent the first example of a transcriptional component regulated by AMP-kinase. Our results suggest a direct link between cellular energy metabolism and gene expression.