BRD7 regulates XBP1s' activity and glucose homeostasis through its interaction with the regulatory subunits of PI3K Academic Article uri icon

Overview

MeSH Major

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Glucose
  • Phosphatidylinositol 3-Kinase
  • Transcription Factors

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.

publication date

  • July 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4079724

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2014.04.006

PubMed ID

  • 24836559

Additional Document Info

start page

  • 73

end page

  • 84

volume

  • 20

number

  • 1