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. Author manuscript; available in PMC: 2011 Jun 1.
Published in final edited form as: Expert Opin Ther Targets. 2010 Jun;14(6):611–620. doi: 10.1517/14728222.2010.487066

Figure 1. Activation of Par-4 leads to apoptosis in PC.

Figure 1

Par-4 is under multiple controls the major ones being mutations in kras along with Akt, Bcl-2, and NF-kB over expression. Akt suppresses Par-4 through phosphorylation and promoting 14-3-3 binding that restricts Par-4 in the cytoplasm. Akt also blocks T155 phosphorylation by PKA in cancer cells. Elevated NF-kB in cancer cells can induce Bcl2 that is known to down-regulate PAR-4. Chemopreventive agent B-DIM can activate Par-4 and also induce Par-4 nuclear translocation by down regulating NF-kB (consequently suppressing Bcl-2) and inhibition of Akt. Apog2 and TW-37 (small molecule inhibitors of Bcl-2) induce Par-4 that ultimately leads to apoptosis. Par-4 can also transduce classical apoptosis pathways like Fas/CD95-mediated cell death by interaction with atypical PKC (ζ). (PC Pancreatic Cancer, B-DIM 3,3’diindolylmethane, Apog2 Apogossypolone, PKA protein kinase A).