Identification, cloning, and expression of human estrogen receptor-α36, a novel variant of human estrogen receptor-α66

Yi Wang Zhao, Xin Tian Zhang, Peng Shen, Brian W. Loggie, Yun Chao Chang, Thomas F. Deuel

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

Abstract

The identification and subsequent cloning of the 66-kDa human estrogen receptor (here termed hER-α66), its 46-kDa splice variant hER-α46, and the closely related hER-β have had a profound impact on the generation of new understanding of estrogen-mediated functions and led to progress in diagnosis and treatment of human breast cancer. However, a persistent problem has been that not all findings previously reported in estrogen-stimulated cell proliferation can be explained through the known properties of the different estrogen receptors described. As the consequence of a search for alternative mechanisms to account for these different findings, we have now identified, cloned, and expressed in HEK 293 cells a previously unrecognized 36-kDa variant of hER-α66, termed hER-α36. hER-α36 differs from hER-α66 since it lacks both transcriptional activation domains (AF-1 and AF-2) but it retains the DNA-binding domain, and partial dimerization and ligand-binding domains of hER-α66. It also contains three myristoylation sites postulated to direct ER-α36 to the plasma membrane. It is concluded that ER-α36 is a unique variant of ER-α66; ER-α36 is predicted to function as a dominant-negative effector of hER-α66-mediated estrogen-responsive gene pathways and has the potential to trigger membrane-initiated mitogenic estrogen signaling.

Original languageEnglish (US)
Pages (from-to)1023-1027
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume336
Issue number4
DOIs
StatePublished - Nov 4 2005

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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