Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Ligand-independent activation of estrogen receptor alpha by XBP-1.

The estrogen receptor (ER) is a member of a large superfamily of nuclear receptors that regulates the transcription of estrogen-responsive genes. Several recent studies have demonstrated that XBP-1 mRNA expression is associated with ERalpha status in breast tumors. However, the role of XBP-1 in ERalpha signaling remains to be elucidated. More recently, two forms of XBP-1 were identified due to its unconventional splicing. We refer to the spliced and unspliced forms of XBP-1 as XBP-1S and XBP-1U, respectively. Here, we report that XBP-1S and XBP-1U enhanced ERalpha-dependent transcriptional activity in a ligand-independent manner. XBP-1S had stronger activity than XBP-1U. The maximal effects of XBP-1S and XBP-1U on ERalpha transactivation were observed when they were co-expressed with full-length ERalpha. SRC-1, the p160 steroid receptor coactivator family member, synergized with XBP-1S or XBP-1U to potentiate ERalpha activity. XBP-1S and XBP-1U bound to the ERalpha both in vitro and in vivo in a ligand-independent fashion. XBP-1S and XBP-1U interacted with the ERalpha region containing the DNA-binding domain. The ERalpha-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, including the N-terminal basic region leucine zipper domain (bZIP) and the C-terminal activation domain. The bZIP-deleted mutants of XBP-1S and XBP-1U completely abolished ERalpha transactivation by XBP-1S and XBP-1U. These findings suggest that XBP-1S and XBP-1U may directly modulate ERalpha signaling in both the absence and presence of estrogen and, therefore, may play important roles in the proliferation of normal and malignant estrogen-regulated tissues.

Pubmed ID: 12954762


  • Ding L
  • Yan J
  • Zhu J
  • Zhong H
  • Lu Q
  • Wang Z
  • Huang C
  • Ye Q


Nucleic acids research

Publication Data

September 15, 2003

Associated Grants


Mesh Terms

  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • DNA-Binding Proteins
  • Electrophoretic Mobility Shift Assay
  • Estrogen Receptor alpha
  • Estrogens
  • Histone Acetyltransferases
  • Humans
  • Ligands
  • Luciferases
  • Nuclear Receptor Coactivator 1
  • Protein Binding
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Response Elements
  • Transcription Factors
  • Transcription, Genetic
  • Transfection