AMP-activated protein kinase regulates gene expression by direct phosphorylation of nuclear proteins.
One of the primary functions of AMP-activated protein kinase (AMPK) is to regulate the metabolic pathways in response to reduced cellular energy charge. Most of the known targets of the kinase are cytoplasmic enzymes involved in both catabolic and anabolic metabolism. In addition, activation of AMPK in many cells results in changes in the pattern of gene expression. Although some of these effects are undoubtedly secondary responses to modified cellular metabolism, it is possible that in addition to its well-characterized function in the cytoplasm, AMPK also directly phosphorylates and regulates proteins involved in gene transcription. There are now several examples of transcription factors, cofactors and components of the transcriptional core machinery that are directly phosphorylated and regulated by AMPK. Here I review these examples and discuss the significance of AMPK activity in the nucleus.
Leff
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Center for Integrative Metabolic and Endocrine Research and the Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA. tleff@med.wayne.edu
D055372:AMP-Activated Protein Kinases; D000123:Acetyltransferases / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D051557:Hepatocyte Nuclear Factor 4; D051548:Histone Acetyltransferases; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism* / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D055372:AMP-Activated Protein Kinases; D000123:Acetyltransferases; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D051548:Histone Acetyltransferases; D009097:Multienzyme Complexes; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C403128:MLX protein, human