Abstract:
:In this study, we determined the ligand-dependent activation function domain 2 (AF-2) of the human vitamin D receptor (hVDR) and characterized it using site-directed mutagenesis. A single mutation at glutamic acid-420 (E420Q) and an additional mutation at leucine-417 (L417A-E420Q) eliminated ligand-dependent transcriptional activation. In addition, lysine-264 was also demonstrated to be vital for ligand-induced transactivation. However, bacterial-overexpressed transcriptional factor IIB (TFIIB) was able to bind to both AF-2 and lysine-264 mutant hVDRs in vitro. The ligand-dependent transactivation via wild type hVDR was interfered with weakly only when a 10-fold molar excess of L417A-E420Q plasmid was co-transfected. This suppressive effect was diminished by introducing an additional mutation at a cysteine residue in the DNA binding domain. Thus, we conclude that the AF-2 domain of the hVDR located between amino acids 417 and 420, as well as lysine-264, are essential for ligand-dependent transactivation, and that TFIIB was not necessary for the function of these two regions of the hVDR. Our finding that AF-2 mutant hVDRs exhibit only very weak suppressive effect may indicate a difference in the molecular mechanism of the VDR-mediated transactivation from other nuclear receptors.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Nakajima S,Yamagata M,Sakai N,Ozono Kdoi
10.1016/s0303-7207(98)00077-xsubject
Has Abstractpub_date
1998-04-30 00:00:00pages
15-24issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(98)00077-Xjournal_volume
139pub_type
杂志文章abstract::cAMP signalling plays a key role in the normal physiology of the pituitary gland, regulating cellular growth and proliferation, hormone production and release. Deregulation of the cAMP signalling pathway has been reported to be a common occurrence in pituitary tumorigenesis. Several mechanisms have been implicated inc...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
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更新日期:2014-07-05 00:00:00
abstract::Evidence is accumulating that environmental chemicals (ECs) including endocrine-disrupting compounds (EDCs) can alter female reproductive development, fertility and onset of menopause. While not as clearly defined as in the male, this set of abnormalities may constitute an Ovarian Dysgenesis Syndrome with at least som...
journal_title:Molecular and cellular endocrinology
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
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更新日期:2006-05-16 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
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更新日期:2016-12-15 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
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更新日期:2006-05-16 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
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更新日期:2018-01-15 00:00:00
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pub_type: 杂志文章
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更新日期:2002-02-22 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2007.10.013
更新日期:2008-02-13 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 临床试验,杂志文章
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更新日期:2007-01-29 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(91)90239-o
更新日期:1991-01-01 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00127-0
更新日期:1998-08-25 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/j.mce.2015.02.018
更新日期:2015-12-15 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2011.02.001
更新日期:2011-04-30 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.08.023
更新日期:2015-11-15 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(90)90134-t
更新日期:1990-10-22 00:00:00
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journal_title:Molecular and cellular endocrinology
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更新日期:2018-04-15 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(97)00141-x
更新日期:1997-09-30 00:00:00
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pub_type: 杂志文章
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更新日期:1983-12-01 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
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更新日期:1985-02-01 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2003.12.011
更新日期:2004-04-15 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.06.036
更新日期:2015-09-15 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2020.111148
更新日期:2020-12-31 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(98)00180-4
更新日期:1998-10-25 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(90)90053-b
更新日期:1990-03-26 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2009.08.015
更新日期:2010-04-29 00:00:00
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journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(99)00106-9
更新日期:1999-08-20 00:00:00
abstract::Transcriptional control of steroid-regulated gene networks by nuclear receptor proteins results in the coordinate expression of a limited number of target genes. Although much is known about the structure and function of steroid receptors, relatively few cell-specific steroid-regulated genes have been isolated and cha...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(95)03481-l
更新日期:1995-02-27 00:00:00