FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors

Tomoshige Kino, Takamasa Ichijo, George P. Chrousos

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We previously reported that tumor necrosis factor α receptor- and Fas-associated FLASH interacts with one of the p160 nuclear receptor coactivators, glucocorticoid receptor-interacting protein (GRIP) 1, at its nuclear receptor-binding (NRB) domain, and that inhibits the transcriptional activity of the glucocorticoid receptor (GR) by interfering with association of GR and GRIP1. Here, we further examined the specificity of FLASH suppressive effect and the physical/functional interactions between this protein and two other p160 family subtypes. The suppressive effect of FLASH on GR transactivation was observed in several cell lines and on the chromatin-integrated mouse mammary tumor virus (MMTV) promoter. FLASH strongly interacted with the NRB domain of the thyroid hormone receptor activator molecule (TRAM) 1, a member of the steroid hormone receptor coactivator (SRC) 3/nuclear receptor coactivator (N-CoA) 3 subtypes, as well as with SRC2/N-CoA2 p160 coactivator GRIP1, while its interaction with SRC1a, one of the SRC1/N-CoA1 proteins, was faint in yeast two-hybrid assays. Accordingly, FLASH strongly suppressed TRAM1- and GRIP1-induced enhancement of GR-stimulated transactivation of the MMTV promoter in HCT116 cells, while it did not affect SRC1a-induced potentiation of transcription. Furthermore, FLASH suppressed androgen- and progesterone receptor-induced transcriptional activity, but did not influence estrogen receptor-induced transactivation, possibly due to their preferential use of p160 coactivators in HCT116 and HeLa cells. Thus, FLASH differentially suppresses steroid hormone receptor-induced transcriptional activity by interfering with their association with SRC2/N-CoA2 and SRC3/N-CoA3 but not with SRC1/N-CoA1.

Original languageEnglish
Pages (from-to)357-363
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume92
Issue number5
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Fingerprint

Steroid hormones
Nuclear Receptor Coactivator 3
Steroid Receptors
Glucocorticoid Receptors
Hormones
Transcriptional Activation
HCT116 Cells
Mouse mammary tumor virus
Cytoplasmic and Nuclear Receptors
Viruses
Carcinogens
Tumors
Nuclear Receptor Coactivator 2
Nuclear Receptor Coactivators
Association reactions
Two-Hybrid System Techniques
Tumor Necrosis Factor Receptors
Androgen Receptors
Progesterone Receptors
Transcription

Keywords

  • FLASH
  • LXXLL motif
  • Nuclear receptor-binding domain
  • p160 coactivators
  • Steroid hormone receptors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors. / Kino, Tomoshige; Ichijo, Takamasa; Chrousos, George P.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 92, No. 5, 12.2004, p. 357-363.

Research output: Contribution to journalArticle

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