Understanding the non-canonical pathways involved in p53-mediated tumor suppression.

In the last three decades since the discovery of p53, it has become increasingly apparent that p53 plays a very important role in tumor suppression. Previously, it was thought that the tumor suppressive functions lied solely in the canonical p53-mediated apoptosis, cell cycle arrest and senescence. However, more recent research has shown that anti-oncogenic activity of p53 can still occur in the absence of these downstream functions. These results suggest that more non-canonical roles of p53 may have a much larger impact on other p53-regulated programs then initially anticipated. Recently, the non-canonical activities of p53 such as cell metabolism, autophagy and necrosis have been the subject of intense study. p53 affects many aspects of cellular metabolism including catabolism, anabolism and reactive oxygen species levels. p53 has a dual role in autophagy regulation. Initiation of autophagy occurs through direct transcription of pro-autophagy genes and inhibition transpires through a transcription-independent mechanism. The role of p53 in these cellular processes is quite complex and evidence suggests that p53 can play both a pro- and anti-oncogenic role in these non-conical pathways. Despite of more than 60,000 publications on p53 in the literature, the mechanisms for p53-mediated tumor suppression apparently needs to be further elucidated.