Heteromeric complex formation of ASK2 and ASK1 regulates stress-induced signaling

Biochem Biophys Res Commun. 2007 Oct 19;362(2):454-9. doi: 10.1016/j.bbrc.2007.08.006. Epub 2007 Aug 10.


Apoptosis signal-regulating kinase 2 (ASK2) is an interaction partner of the highly related ASK1. Here, we describe a regulatory function of ASK2 in stress signaling-induced cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP). Increased cleavage of caspase-3 and PARP was demonstrated by overexpression as well as knockdown of ASK2 after stress-induction by serum-starvation. We show that ectopically expressed ASK2 homo-oligomerized while endogenous ASK2 and ASK1 formed hetero-oligomers, which decreased upon serum-starvation. Co-expression of ASK2 and ASK1 stabilized these two proteins and reduced starvation-induced caspase-3 activation and degradation of PARP. Analysis of the intracellular localization of ASK2 exhibited a similar localization compared with ASK1 in the nucleus, cytoplasm, and in mitochondria. We propose that ASK2 regulates stress-induced caspase-3 and PARP cleavage in a dose-dependent manner by heteromeric complex formation with ASK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 3 / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Culture Media, Serum-Free / pharmacology
  • Cytoplasm / metabolism
  • Cytoskeleton / metabolism
  • Dimerization
  • HeLa Cells
  • Humans
  • Hydrolysis / drug effects
  • Immunoblotting
  • Immunoprecipitation
  • MAP Kinase Kinase Kinase 5 / chemistry
  • MAP Kinase Kinase Kinase 5 / genetics
  • MAP Kinase Kinase Kinase 5 / metabolism*
  • MAP Kinase Kinase Kinases / chemistry
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Organelles / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Binding
  • RNA Interference
  • Signal Transduction
  • Transfection


  • Culture Media, Serum-Free
  • Poly(ADP-ribose) Polymerases
  • MAP Kinase Kinase Kinase 5
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 6
  • MAP3K5 protein, human
  • Caspase 3