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Protein Modifier SUMO Helps Set Apart Females And Males

Date:
September 3, 2009
Source:
Journal of Clinical Investigation
Summary:
One way in which men and women differ is in their expression of liver proteins that control energy generation and lipid and steroid hormone production and turnover. Researchers have identified a new mechanism -- involving a process known as sumoylation -- underlying this differential expression of proteins in male and female mice. They also suggest drugs that may prevent estrogen-induced intrahepatic cholestasis, the most common liver disease during pregnancy.
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One way in which men and women differ is in their expression of liver proteins that control a large number of whole-body processes such as energy generation and lipid and steroid hormone production and turnover.

Now, Walter Wahli and colleagues, at the University of Lausanne, Switzerland, have identified a new mechanism underlying this differential expression of proteins in male and female mice. The research appears in the Sept. 1, 2009 issue of the Journal of Clinical Investigation.

The protein PPAR-alpha is able to enter the nucleus, where it acts to control the expression of a large number of genes. In the study, PPAR-alpha was found to repress the expression of many liver genes responsible for making proteins involved in immunity and steroid production and turnover only in female mice. One of the genes most strongly repressed in female mice by PPAR-alpha was Cyp7b1, which generates a protein involved in drug breakdown and the generation of cholesterol, steroids, and other fats. Detailed analysis revealed the mechanism by which PPAR-alpha repressed Cyp7b1 expression, it was modified by a process known as sumoylation.

Importantly, this only occurred in female mice. As PPAR-alpha–mediated repression protected female mice from estrogen-induced intrahepatic cholestasis, the most common liver disease during pregnancy, the authors suggest that PPAR-alpha agonists might provide a new approach to prevent this disease.


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The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nicolas Leuenberger, Sylvain Pradervand, and Walter Wahli. Sumoylated PPAR-alpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI39019

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Journal of Clinical Investigation. "Protein Modifier SUMO Helps Set Apart Females And Males." ScienceDaily. ScienceDaily, 3 September 2009. <www.sciencedaily.com/releases/2009/09/090901172826.htm>.
Journal of Clinical Investigation. (2009, September 3). Protein Modifier SUMO Helps Set Apart Females And Males. ScienceDaily. Retrieved August 30, 2015 from www.sciencedaily.com/releases/2009/09/090901172826.htm
Journal of Clinical Investigation. "Protein Modifier SUMO Helps Set Apart Females And Males." ScienceDaily. www.sciencedaily.com/releases/2009/09/090901172826.htm (accessed August 30, 2015).

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