Woodgate A, Walton M, MacGibbon G A, Dragunow M
The Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):211-6. doi: 10.1016/s0169-328x(99)00027-3.
We have developed a model of nerve cell death based on the toxicity of okadaic acid, a compound that triggers apoptosis in PC12 cells via a protein synthesis-dependent mechanism. The cell death process is accompanied by induction of JunB, c-Jun, JunD and Fos proteins. Phosphorylation-specific antibodies were used to demonstrate that c-Jun is phosphorylated at serine 63 and serine 73. Electrophoretic gel mobility shift and pAP1-Luc luciferase assays showed that expression of ITFs is associated with increases in AP-1 binding and in AP-1 transcriptional activity. In addition, dose response and time course studies provided strong correlative evidence that Fos and Jun proteins are involved in the apoptotic death cascades. Thus, this model provides a useful system to investigate the role of inducible transcription factor proteins in apoptosis.
