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

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 transcr...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-10, Vol.276 (42), p.38341-38344
Main Authors: Yang, W, Hong, Y H, Shen, X Q, Frankowski, C, Camp, H S, Leff, T
Format: Article
Language:English
Subjects:
Amino Acid Sequence
AMP-Activated Protein Kinases
AMP-kinase
Animals
Blotting, Western
Cell Nucleus - metabolism
Cricetinae
Dose-Response Relationship, Drug
Humans
Molecular Sequence Data
Multienzyme Complexes - metabolism
Mutation
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
p300 protein
peroxisome proliferator-activated receptor ^g
Phosphorylation
Plasmids - metabolism
Protein-Serine-Threonine Kinases - metabolism
Receptors, Retinoic Acid - metabolism
Retinoid X Receptors
Sequence Homology, Amino Acid
Signal Transduction
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription Factors - metabolism
Transcription, Genetic
Transfection
Two-Hybrid System Techniques
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Summary: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 E1a, 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.
ISSN:0021-9258
DOI:10.1074/jbc.C100316200