Two Variants of a Gut Protein Seen to Have Opposite Roles in Colitis and Colon Cancer Risk

Two Variants of a Gut Protein Seen to Have Opposite Roles in Colitis and Colon Cancer Risk
A team of researchers at the University of California, Riverside, found that a tight control of the levels of two forms of the same protein, hepatocyte nuclear factor 4-alpha (HNF4-α), is critical to prevent intestinal diseases. The findings are described in the study, "Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer," published in the journal eLife. The HNF4-α gene has been linked to several gastrointestinal disorders, including colitis and colon cancer. A mutation in a single nucleotide in HNF4-α has been associated with ulcerative colitis. However, there are two variants of this protein, P1-HNF4-α (P1) and P2-HNF4-α (P2), and the role of each variant in normal and malignant colon function is not known. Researchers, led by Frances M. Sladek, a professor of cell biology at UC Riverside, studied the role and distribution of both isoforms, and found that a tight balance of P1 and P2 is critical to reduce the risk of colitis and colon cancer. “P1 and P2 have been conserved between mice and humans for 70 million years,” Professor Sladek said in a press release. “Both isoforms are important and we want to keep an appropriate balance between them in our gut by avoiding foods that would disrupt this balance and consuming foods that help preserve it. What these foods are is our next focus in the lab.” Although HNF4α is expressed in the liver, kidney, pancreas, and stomach, the intestine is the only adult tissue th
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