Tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner

Metabolic changes in cancer have been observed for almost a century. The mechanisms underlying these changes have begun to emerge from the recent studies implicating the tumor suppressor p53 in multiple metabolic pathways. The ability of p53 to regulate metabolism may also play important roles in the physiology of normal cells and organs. Here we demonstrate that p53 lowers bile acid (BA) levels under both normal and stressed conditions primarily through up-regulating expression of small heterodimer partner, a critical inhibitor of BA synthesis. Our results uncover a unique metabolic regulatory axis that unexpectedly couples p53 to BA homeostasis. Our results also warrant future studies to investigate a possible role of this axis in the tumor suppression by p53, because excessive quantities of BAs are cytotoxic and can cause liver damage and promote gastrointestinal cancers.