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The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are the two most important components of cellular mechanisms for protein degradation.In the present study we investigated the functional relationship of the two systems and the interactional role of p53 in vitro.Our study showed that the proteasome inhibitor lactacystin induced an increase in p53 level and autophagy activity, whereas inhibition of p53 by pifithrin-α or small interference RNA (siRNA) of p53 attenuated the autophagy induction and increased protein aggregation.