NDLI: Ligand-independent activation of estrogen receptor α by XBP-1

Content Provider	PubMed Central
Author	Ding, Lihua Yan, Jinghua Zhu, Jianhua Zhong, Hongjun Lu, Qiujun Wang, Zonghua Huang, Cuifen Ye, Qinong
Copyright Year	2003
Abstract	The estrogen receptor (ER) is a member of a large superfamily of nuclear receptors that regulates the transcription of estrogen-responsive genes. Several recent studies have demonstrated that XBP-1 mRNA expression is associated with ERα status in breast tumors. However, the role of XBP-1 in ERα signaling remains to be elucidated. More recently, two forms of XBP-1 were identified due to its unconventional splicing. We refer to the spliced and unspliced forms of XBP-1 as XBP-1S and XBP-1U, respectively. Here, we report that XBP-1S and XBP-1U enhanced ERα-dependent transcriptional activity in a ligand-independent manner. XBP-1S had stronger activity than XBP-1U. The maximal effects of XBP-1S and XBP-1U on ERα transactivation were observed when they were co-expressed with full-length ERα. SRC-1, the p160 steroid receptor coactivator family member, synergized with XBP-1S or XBP-1U to potentiate ERα activity. XBP-1S and XBP-1U bound to the ERα both in vitro and in vivo in a ligand-independent fashion. XBP-1S and XBP-1U interacted with the ERα region containing the DNA-binding domain. The ERα-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, including the N-terminal basic region leucine zipper domain (bZIP) and the C-terminal activation domain. The bZIP-deleted mutants of XBP-1S and XBP-1U completely abolished ERα transactivation by XBP-1S and XBP-1U. These findings suggest that XBP-1S and XBP-1U may directly modulate ERα signaling in both the absence and presence of estrogen and, therefore, may play important roles in the proliferation of normal and malignant estrogen-regulated tissues.
Related Links	http://dx.doi.org/10.1093/nar/gkg731
Ending Page	5274
Page Count	9
Starting Page	5266
File Format	PDF
ISSN	13624962
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	18
Volume Number	31
Language	English
Publisher	Oxford University Press
Publisher Date	2003-09-15
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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