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Cell Metab. 2014 Jul 1;20(1):73-84. doi: 10.1016/j.cmet.2014.04.006. Epub 2014 May 15.

BRD7 regulates XBP1s' activity and glucose homeostasis through its interaction with the regulatory subunits of PI3K.

Author information

1
Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: sangwon.park@childrens.harvard.edu.
2
Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
Department of System Biology, Harvard Medical School, Boston, MA 02115, USA; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
4
Department of System Biology, Harvard Medical School, Boston, MA 02115, USA; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Medicine, Weill Cornell Medical College, New York City, NY 10065, USA.
5
Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: umut.ozcan@childrens.harvard.edu.

Erratum in

  • Cell Metab. 2014 Dec 2;20(6):1088.

Abstract

Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family that is known to play a role as tumor suppressors. Here, we show that BRD7 is a component of the unfolded protein response (UPR) signaling through its ability to regulate X-box binding protein 1 (XBP1) nuclear translocation. BRD7 interacts with the regulatory subunits of phosphatidylinositol 3-kinase (PI3K) and increases the nuclear translocation of both p85α and p85β and the spliced form of XBP1 (XBP1s). Deficiency of BRD7 blocks the nuclear translocation of XBP1s. Furthermore, our in vivo studies have shown that BRD7 protein levels are reduced in the liver of obese mice, and reinstating BRD7 levels in the liver restores XBP1s nuclear translocation, improves glucose homeostasis, and ultimately reduces the blood glucose levels in the obese and diabetic mouse models.

PMID:
24836559
PMCID:
PMC4079724
DOI:
10.1016/j.cmet.2014.04.006
[Indexed for MEDLINE]
Free PMC Article

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