We generated A21-13 cells expressing p14 ARF in the presence of doxycycline in order to examine the stability of p14 ARF protein. The effects of proteasome inhibitor MG132 on p14 ARF protein stabilization were detectable using our experimental procedure. Introduction of mutant p53 did not affect MG132-mediated p14 ARF protein stabilization. We found that phorbol ester TPA (12-o-tetradecanoyl-phorbol 13-acetate) stabilized p14 ARF protein and that p53 status had no effect on TPA-mediated stabilization. TPA-mediated stabilization was abolished by staurosporine but not by lovastatin or U0126. We further investigated which isoforms of PKC were involved in TPA-mediated p14 ARF stabilization using short-interference RNA. Knockdown of PKCα, but not PKCδ, attenuated TPA-mediated p14 ARF stabilization. These findings suggest that PKCα is involved in TPA-mediated stabilization of p14 ARF protein, and this effect of TPA was not affected by the Ras/MAPK pathway or p53 status. Our results are indicative of a novel role of PKC in p14 ARF protein stability.