The object of this study was to investigate the molecular mechanisms mediating TNF alpha-induced apoptosis and autophagy in L929 cells. Herein, we found that the treatment of L929 cells with TNF alpha caused a time-dependent increase in p53 activity. The inhibition of p53 activation reduced TNF alpha-induced apoptosis and autophagy that were accompanied by the decrease in the levels of A1F, Beclin1 and LC3. Subsequently, TNF alpha activated ERK, JNK and p38 in apoptosis and autopahgy, in which ERK/JNK played a promoting role whereas p38 played an inhibiting one. In addition, TNF alpha-induced p53 activation was reduced by ERK or but it was not affected by p38 inhibition. Further data showed that the inhibition of JNK inhibition, autophagy reduced TNF alpha-induced apoptosis in L929 cells. In conclusion, these results demonstrate that TNFa-induced MAPKs mediate p53 activation in apoptotic and autophagic cell death, as well as autophagy may amplify apoptosis when associated with a death signaling pathway. (c) 2008 Elsevier Inc. All rights reserved.