The JNK binding domain of islet-brain 1 inhibits IL-1 induced JNK activity and apoptosis but not the transcription of key proapoptotic or protective genes in insulin-secreting cell lines

Cytokine. 2003 Oct;24(1-2):13-24. doi: 10.1016/s1043-4666(03)00242-4.


The stress-activated protein kinase c-Jun NH2-terminal kinase (JNK) is a central signal for interleukin-1beta (IL-1beta)-induced apoptosis in insulin-producing beta-cells. The cell-permeable peptide inhibitor of JNK (JNKI1), that introduces the JNK binding domain (JBD) of the scaffold protein islet-brain 1 (IB1) inside cells, effectively prevents beta-cell death caused by this cytokine. To define the molecular targets of JNK involved in cytokine-induced beta-cell apoptosis we investigated whether JNKI1 or stable expression of JBD affected the expression of selected pro- and anti-apoptotic genes induced in rat (RIN-5AH-T2B) and mouse (betaTC3) insulinoma cells exposed to IL-1beta. Inhibition of JNK significantly reduced phosphorylation of the specific JNK substrate c-Jun (p<0.05), IL-1beta-induced apoptosis (p<0.001), and IL-1beta-mediated c-fos gene expression. However, neither JNKI1 nor JBD did influence IL-1beta-induced NO synthesis or iNOS expression or the transcription of the genes encoding mitochondrial manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase rho (GSTrho), heat shock protein (HSP) 70, IL-1beta-converting enzyme (ICE), caspase-3, apoptosis-inducing factor (AIF), Bcl-2 or Bcl-xL. We suggest that the anti-apoptotic effect of JNK inhibition by JBD is independent of the transcription of major pro- and anti-apoptotic genes, but may be exerted at the translational or posttranslational level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis / physiology*
  • Binding Sites
  • Insulin / metabolism
  • Interleukin-1 / metabolism
  • Islets of Langerhans / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nitric Oxide
  • Nitric Oxide Synthase / metabolism
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Rats
  • Trans-Activators / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Insulin
  • Interleukin-1
  • Mapk8ip protein, mouse
  • Mapk8ip1 protein, rat
  • Nuclear Proteins
  • Trans-Activators
  • Nitric Oxide
  • Nitric Oxide Synthase
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases