ASK1-JNK signaling cascade mediates Ad-ST13-induced apoptosis in colorectal HCT116 cells

J Cell Biochem. 2010 Jun 1;110(3):581-8. doi: 10.1002/jcb.22551.

Abstract

ST13, a co-factor of heat shock protein, has shown potential antitumor efficacy for colorectal cancer in our previous study. However, the molecular mechanisms governing ST13-induced apoptosis are poorly understood. Here, we demonstrate that Ad-ST13 (ST13 mediated by adenovirus) activates apoptosis signal-regulated kinase (ASK1) and c-Jun N-terminal kinase (JNK) but not p38 (mitogen-activated protein kinase) in human colorectal HCT116 cells. Ad-ST13 also increases extracellular-regulated kinase (ERK) phosphorylation levels, but the change is due to adenovirus replication. Overexpression of ST13 also increases the transcription activity of AP-1. Blocking ASK1-JNK pathway affects Ad-ST13-mediated colorectal cell apoptosis, decreases the release of cytochrome c in cytoplasm and caspase activation. Because ASK1 is known to contain a tetratricopeptide repeat (TPR)-acceptor site and ST13 has TPR domain, we found the interaction between ST13 and ASK1. These results strongly indicate Ad-ST13 triggers colorectal cell apoptosis via ASK1-JNK signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / metabolism
  • Apoptosis / physiology*
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / therapy
  • Genetic Therapy / methods*
  • HCT116 Cells
  • Humans
  • Immunoprecipitation
  • MAP Kinase Kinase 4 / metabolism*
  • MAP Kinase Kinase Kinase 5 / metabolism*
  • Signal Transduction / physiology*
  • Transcriptional Activation
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • ST13 protein, human
  • Tumor Suppressor Proteins
  • MAP Kinase Kinase Kinase 5
  • MAP3K5 protein, human
  • MAP Kinase Kinase 4