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A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA.

One class of the nuclear receptor AF-2 coactivator complexes contains the SRC-1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a subfamily of RNA-binding DEAD-box proteins (p72/p68) as a human estrogen receptor alpha (hER alpha) coactivator in the complex containing these factors. p72/p68 interacted with both the AD2 of any SRC-1/TIF2 family protein and the hER alpha A/B domain, but not with any other nuclear receptor tested. p72/p68, TIF2 (SRC-1) and SRA were co-immunoprecipitated with estrogen-bound hER alpha in MCF7 cells and in partially purified complexes associated with hER alpha from HeLa nuclear extracts. Estrogen induced co-localization of p72 with hER alpha and TIF2 in the nucleus. The presence of p72/p68 potentiated the estrogen-induced expression of the endogenous pS2 gene in MCF7 cells. In a transient expression assay, a combination of p72/p68 with SRA and one TIF2 brought an ultimate synergism to the estrogen-induced transactivation of hER alpha. These findings indicate that p72/p68 acts as an ER subtype-selective coactivator through ER alpha AF-1 by associating with the coactivator complex to bind its AF-2 through direct binding with SRA and the SRC-1/TIF2 family proteins.

Pubmed ID: 11250900


  • Watanabe M
  • Yanagisawa J
  • Kitagawa H
  • Takeyama K
  • Ogawa S
  • Arao Y
  • Suzawa M
  • Kobayashi Y
  • Yano T
  • Yoshikawa H
  • Masuhiro Y
  • Kato S


The EMBO journal

Publication Data

March 15, 2001

Associated Grants


Mesh Terms

  • Amino Acid Motifs
  • Cell Compartmentation
  • Estradiol
  • Estrogen Receptor Modulators
  • Estrogen Receptor alpha
  • Estrogens
  • HeLa Cells
  • Histone Acetyltransferases
  • Humans
  • Ligands
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 2
  • Protein Binding
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Transcription Factors
  • Transcriptional Activation
  • Tumor Suppressor Proteins
  • Two-Hybrid System Techniques