Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66

Biochem Biophys Res Commun. 2005 Nov 4;336(4):1023-7. doi: 10.1016/j.bbrc.2005.08.226.

Abstract

The identification and subsequent cloning of the 66-kDa human estrogen receptor (here termed hER-alpha66), its 46-kDa splice variant hER-alpha46, and the closely related hER-beta 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-alpha66, termed hER-alpha36. hER-alpha36 differs from hER-alpha66 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-alpha66. It also contains three myristoylation sites postulated to direct ER-alpha36 to the plasma membrane. It is concluded that ER-alpha36 is a unique variant of ER-alpha66; ER-alpha36 is predicted to function as a dominant-negative effector of hER-alpha66-mediated estrogen-responsive gene pathways and has the potential to trigger membrane-initiated mitogenic estrogen signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cloning, Molecular
  • Estrogen Receptor alpha / biosynthesis*
  • Estrogen Receptor alpha / genetics
  • Humans
  • Molecular Sequence Data
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Protein Structure, Tertiary

Substances

  • Estrogen Receptor alpha
  • Protein Isoforms