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

Autor: N.A. Andersen, Philippe Dupraz, Thomas Mandrup-Poulsen, N. Sandhu, Allan E. Karlsen, Anne Oberson, Bernard Thorens, M.A. Nikulina, Z. Shamim, Christophe Bonny
Rok vydání: 2003
Předmět:
Zdroj: Cytokine. 24:13-24
ISSN: 1043-4666
DOI: 10.1016/s1043-4666(03)00242-4
Popis: 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
Databáze: OpenAIRE