p53 mutations affect cancer cell metabolism

The loss of the tumour suppressor protein p53 might underlie cancer cells' ability to undergo a metabolic switch that supports rapid proliferation in the face of limited availability of nutrients. This finding, reported online this week in Nature Cell Biology, reinforces the importance of p53 loss in the development of cancer.

p53 is known to modulate cancer cell metabolism by regulating gene transcription within the nucleus. Xiaolu Yang and colleagues recognized that cells lacking functional p53 consumed large quantities of glucose through the ox-PPP pathway, which supports the biosynthesis of new cellular building blocks from glucose and is critical for cancer cell proliferation.

They found that p53 interacts with a key enzyme in the ox-PPP pathway outside of the nucleus. The authors conclude that p53 normally inhibits this enzyme to block the ox-PPP pathway, but that loss of p53 removes this block and activates the pathway. In an accompanying News & Views article, Eyal Gottlieb notes that this "effect of p53…is intriguing as it proposes a catalytic (enzymatic) role for p53 in the cytosol."