Activated glucocorticoid receptor interacts with the INHAT component Set/TAF-Iβ and releases it from a glucocorticoid-responsive gene promoter, relieving repression: Implications for the pathogenesis of glucocorticoid resistance in acute undifferentiated leukemia with Set-Can translocation

Takamasa Ichijo, George P. Chrousos, Tomoshige Kino

Research output: Contribution to journalArticle

25 Citations (Scopus)


Set/template-activating factor (TAF)-Iβ, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Iβ interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Iβ was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Iβ from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Iβ acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids.

Original languageEnglish
Pages (from-to)19-31
Number of pages13
JournalMolecular and Cellular Endocrinology
Issue number1-2
Publication statusPublished - 13 Feb 2008
Externally publishedYes



  • Glucocorticoid receptor
  • Histone acetylation
  • Inhibitor of histone acetyltransferases complex
  • Leukemia
  • Set-Can translocation
  • Set/TAF-Iβ

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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