The nuclear protein Artemis promotes AMPK activation by stabilizing the LKB1-AMPK complex

Biochem Biophys Res Commun. 2012 Nov 2;427(4):790-5. doi: 10.1016/j.bbrc.2012.09.140. Epub 2012 Oct 5.

Abstract

AMP-activated protein kinase (AMPK) is a hetero-trimeric Ser/Thr kinase composed of a catalytic α subunit and regulatory β and γ subunits; it functions as an energy sensor that controls cellular energy homeostasis. In response to an increased cellular AMP/ATP ratio, AMPK is activated by phosphorylation at Thr172 in the α-subunit by upstream AMPK kinases (AMPKKs), including tumor suppressor liver kinase B1 (LKB1). To elucidate more precise molecular mechanisms of AMPK activation, we performed yeast two-hybrid screening and isolated the complementary DNA (cDNA) encoding the nuclear protein Artemis/DNA cross-link repair 1C (DCLRE1C) as an AMPKα2-binding protein. Artemis was found to co-immunoprecipitate with AMPKα2, and the co-localization of Artemis with AMPKα2 in the nucleus was confirmed by immunofluorescence staining in U2OS cells. Moreover, over-expression of Artemis enhanced the phosphorylation of AMPKα2 and the AMPK substrate acetyl-CoA carboxylase (ACC). Conversely, RNAi-mediated knockdown of Artemis reduced AMPK and ACC phosphorylation. In addition, Artemis markedly increased the physical association between AMPKα2 and LKB1. Taken together, these results suggest that Artemis functions as a positive regulator of AMPK signaling by stabilizing the LKB1-AMPK complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases / biosynthesis*
  • AMP-Activated Protein Kinases / metabolism
  • Cell Line, Tumor
  • DNA-Binding Proteins
  • Endonucleases
  • Enzyme Stability
  • Humans
  • Immunoprecipitation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • PRKAA2 protein, human
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • DCLRE1C protein, human
  • Endonucleases