Role of the hinge region of glucocorticoid receptor for HEXIM1-mediated transcriptional repression

Noritada Yoshikawa, Noriaki Shimizu, Motoaki Sano, Kei Ohnuma, Satoshi Iwata, Osamu Hosono, Keiichi Fukuda, Chikao Morimoto, Hirotoshi Tanaka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We previously reported that HEXIM1 (hexamethylene bisacetamide-inducible protein 1), which suppresses transcription elongation via sequestration of positive transcription elongation factor b (P-TEFb) using 7SK RNA as a scaffold, directly associates with glucocorticoid receptor (GR) to suppress glucocorticoid-inducible gene activation. Here, we revealed that the hinge region of GR is essential for its interaction with HEXIM1, and that oxosteroid receptors including GR show sequence homology in their hinge region and interact with HEXIM1, whereas the other members of nuclear receptors do not. We also showed that HEXIM1 suppresses GR-mediated transcription in two ways: sequestration of P-TEFb by HEXIM1 and direct interaction between GR and HEXIM1. In contrast, peroxisome proliferator-activated receptor γ-dependent gene expression is negatively modulated by HEXIM1 solely via sequestration of P-TEFb. We, therefore, conclude that HEXIM1 may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including GR and contribute to fine-tuning of, for example, glucocorticoid-mediated biological responses.

Original languageEnglish
Pages (from-to)44-49
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number1
DOIs
Publication statusPublished - 2008 Jun 20

Keywords

  • Elongation
  • Glucocorticoid
  • HEXIM1
  • Hinge region
  • Nuclear receptor
  • P-TEFb
  • RNA
  • Transcription

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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