MUC1 activates JNK1 and inhibits apoptosis under genotoxic stress

Biochem Biophys Res Commun. 2013 Oct 11;440(1):179-83. doi: 10.1016/j.bbrc.2013.09.055. Epub 2013 Sep 18.

Abstract

The MUC1 transmembrane glycoprotein is aberrantly overexpressed in diverse human carcinomas and has been shown to inhibit apoptosis induced by genotoxic agents. In the present work, we report that MUC1 binds to and activates JNK1, an important member of the mitogen-activated protein kinases (MAPK) superfamily. The physical interaction between MUC1 cytoplasmic domain (MUC1-CD) and JNK1 was established by GST-pull-down assay in vitro and co-immunoprecipitation assay in vivo. We show that MUC1 activates JNK1 and inhibits cisplatin-induced apoptosis in human colon cancer HCT116 cells. Pharmacological inhibition of JNK or knockdown of JNK significantly reduces the ability of MUC1 to inhibit cisplatin-induced apoptosis. Together, our data indicate that MUC1 can inhibit apoptosis via activating JNK1 pathway in response to genotoxic anticancer agents.

Keywords: Apoptosis; DNA damage; JNK; MUC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cisplatin / pharmacology*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • DNA Damage / drug effects
  • Enzyme Activation
  • HCT116 Cells
  • Humans
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Mucin-1 / chemistry
  • Mucin-1 / metabolism*
  • Phosphorylation
  • Protein Binding
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • MUC1 protein, human
  • Mucin-1
  • Mitogen-Activated Protein Kinase 8
  • Cisplatin