• Register
Forgot Password

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


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1.

The estrogen receptor (ER) is an important regulator of growth and differentiation of breast epithelium. Transactivation by ER depends on a leucine-rich motif, which constitutes a ligand-regulated binding site for steroid receptor coactivators (SRCs). Cyclin D1 is frequently amplified in breast cancer and can activate ER through direct binding. We show here that cyclin D1 also interacts in a ligand-independent fashion with coactivators of the SRC-1 family through a motif that resembles the leucine-rich coactivator binding motif of nuclear receptors. By acting as a bridging factor between ER and SRCs, cyclin D1 can recruit SRC-family coactivators to ER in the absence of ligand. A cyclin D1 mutant that binds to ER but fails to recruit coactivators preferentially interferes with ER activation in breast cancer cells that have high levels of cyclin D1. These data support that cyclin D1 contributes significantly to ER activation in breast cancers in which the protein is overexpressed. Our present results reveal a novel route of coactivator recruitment to ER and establish a direct role for cyclin D1 in regulation of transcription.

Pubmed ID: 9832502


  • Zwijsen RM
  • Buckle RS
  • Hijmans EM
  • Loomans CJ
  • Bernards R


Genes & development

Publication Data

November 15, 1998

Associated Grants


Mesh Terms

  • Animals
  • COS Cells
  • Cyclin D1
  • Gene Expression Regulation, Neoplastic
  • Histone Acetyltransferases
  • Humans
  • Ligands
  • Mutation
  • Nuclear Proteins
  • Nuclear Receptor Coactivator 1
  • Protein Binding
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured