AMP-activated protein kinase is a positive regulator of poly(ADP-ribose) polymerase.
AMPK acts as a cellular fuel gauge and responds to decreased cellular energy status by inhibiting ATP-consuming pathways and increasing ATP-synthesis. The aim of this study was to examine the role of AMPK in modulating poly(ADP-ribose) polymerase (PARP), a nuclear enzyme involved in maintaining chromatin structure and DNA repair. HT-29 cells infected with constitutively active AMPK demonstrated increased PARP automodification and an increase in bioNAD incorporation. AMPK and PARP co-immunoprecipitated under basal conditions and in response to H(2)O(2), suggesting a physical interaction under both resting and stress-induced conditions. Incubation of PARP with purified AMPK resulted in the phosphorylation of PARP; and the inclusion of AMP as an AMPK activator potentiated PARP phosphorylation. Using immobilized PARP, the incorporation of bioNAD by PARP was dramatically increased following the addition of AMPK. These data suggest a novel role for AMPK in regulating PARP activity through a direct interaction involving phosphorylation.
Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
John W
JW
Walker
Humberto B
HB
Jijon
Karen L
KL
Madsen
D055372:AMP-Activated Protein Kinases; D017209:Apoptosis; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013997:Time Factors
D009097:Multienzyme Complexes; D011065:Poly(ADP-ribose) Polymerases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases