Editors' ChoiceNuclear Receptors

It’s a Knock Out

Science Signaling  02 Dec 2008:
Vol. 1, Issue 48, pp. ec414
DOI: 10.1126/scisignal.148ec414

The steroid receptor coactivator 2 (SRC-2) protein is well known for its function in activating transcription as a partner of the progesterone receptor. Chopra et al. describe analysis of mice lacking SRC-2 that reveals a role for the coactivator in glucose metabolism and expression of the gene encoding glucose-6-phosphatase. The knockout animals have similar characteristics to those of humans with Von Gierke’s disease, which is caused by mutations in glucose-6-phosphatase. In this context, it appears that SRC-2 may function to assist retinoid-related orphan receptor alpha (a nuclear hormone receptor related to the progesterone receptor), which binds to the promoter of the glucose-6-phosphatase gene and enhances its expression.

A. R. Chopra, J.-F. Louet, P. Saha, J. An, F. DeMayo, J. Xu, B. York, S. Karpen, M. Finegold, D. Moore, L. Chan, C. B. Newgard, B. W. O’Malley, Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke’s disease. Science 322, 1395–1399 (2008). [Abstract] [Full Text]