Identification, cloning, and expression of human estrogen receptor-{alpha}36, a novel variant of human estrogen receptor-{alpha}66

Journal Article · Fri Nov 04 00:00:00 EST 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.08.226· OSTI ID:20713412

Zhaoyi, Wang ^[1]; Xintian, Zhang ^[1]; Peng, Shen ^[1]; Loggie, Brian W ^[1]; Yunchao, Chang ^[2]; Deuel, Thomas F ^[2]

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1. Cancer Center, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States)
2. Departments of Molecular and Experimental Medicine and Cell Biology, Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037 (United States)

The identification and subsequent cloning of the 66-kDa human estrogen receptor (here termed hER-{alpha}66), its 46-kDa splice variant hER-{alpha}46, 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-{alpha}66, termed hER-{alpha}36. hER-{alpha}36 differs from hER-{alpha}66 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-{alpha}66. It also contains three myristoylation sites postulated to direct ER-{alpha}36 to the plasma membrane. It is concluded that ER-{alpha}36 is a unique variant of ER-{alpha}66; ER-{alpha}36 is predicted to function as a dominant-negative effector of hER-{alpha}66-mediated estrogen-responsive gene pathways and has the potential to trigger membrane-initiated mitogenic estrogen signaling.

• OSTI ID: 20713412
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 336, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2005.08.226; PII: S0006-291X(05)01951-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOMAS
CELL PROLIFERATION
CLONING
DIAGNOSIS
DIMERIZATION
DNA
ESTROGENS
GENES
LIGANDS
MAMMARY GLANDS
RECEPTORS