Tumor suppressor p53 regulates bile acid homeostasis via small heterodimer partner

Dae Hwan Kim, Jae W. Lee

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12266-12270
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number30
DOIs
StatePublished - Jul 26 2011

ASJC Scopus subject areas

  • General

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