Identification, cloning, and expression of human estrogen receptor-α36, a novel variant of human estrogen receptor-α66
Identification, cloning, and expression of human estrogen receptor-α36, a novel variant of human estrogen receptor-α66
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DOI：
10.1016/j.bbrc.2005.08.226
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发表时间：
2005-11-04
影响因子：
3.1
通讯作者：
Deuel, TF
中科院分区：
文献类型：
--
作者：
Wang, ZY;Zhang, XT;Deuel, TF
The identification and subsequent cloning of the 66-kDa human estrogen receptor (here termed hER-u66), 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-oc66 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. (c) 2005 Elsevier Inc. All rights reserved.
