IB1 reduces cytokine-induced apoptosis of insulin-secreting cells

J Biol Chem. 2000 Jun 2;275(22):16466-72. doi: 10.1074/jbc.M908297199.


IB1/JIP-1 is a scaffold protein that interacts with upstream components of the c-Jun N-terminal kinase (JNK) signaling pathway. IB1 is expressed at high levels in pancreatic beta cells and may therefore exert a tight control on signaling events mediated by JNK in these cells. Activation of JNK by interleukin 1 (IL-1beta) or by the upstream JNK constitutive activator DeltaMEKK1 promoted apoptosis in two pancreatic beta cell lines and decreased IB1 content by 50-60%. To study the functional consequences of the reduced IB1 content in beta cell lines, we used an insulin-secreting cell line expressing an inducible IB1 antisense RNA that lead to a 38% IB1 decrease. Reducing IB1 levels in these cells increased phosphorylation of c-Jun and increased the apoptotic rate in presence of IL-1beta. Nitric oxide production was not stimulated by expression of the IB1 antisense RNA. Complementary experiments indicated that overexpression of IB1 in insulin-producing cells prevented JNK-mediated activation of the transcription factors c-Jun, ATF2, and Elk1 and decreased IL-1beta- and DeltaMEKK1-induced apoptosis. These data indicate that IB1 plays an anti-apoptotic function in insulin-producing cells probably by controlling the activity of the JNK signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Doxycycline / pharmacology
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / radiation effects
  • Nitric Oxide / metabolism
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Antisense / genetics
  • Trans-Activators / physiology*
  • Ultraviolet Rays


  • Insulin
  • Interleukin-1
  • Nuclear Proteins
  • RNA, Antisense
  • Trans-Activators
  • Nitric Oxide
  • Protein Serine-Threonine Kinases
  • Glucose
  • Doxycycline