MODULATION OF TRANSCRIPTIONAL ACTIVATION BY LIGAND-DEPENDENT PHOSPHORYLATION OF THE HUMAN ESTROGEN RECEPTOR-A/B REGION

被引:375
作者
ALI, S
METZGER, D
BORNERT, JM
CHAMBON, P
机构
[1] Laboratoire de Genetique Moleculaire, Unite 184 de Biologie Moleculaire, Inst Chimie Biolog/Faculte Medecine, 67085 Strasbourg Cedex
关键词
ANTIESTROGENS; ESTROGEN RECEPTOR; PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVATION FUNCTION;
D O I
10.1002/j.1460-2075.1993.tb05756.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Using a transient co-transfection system, we show that the human oestrogen receptor (hER) becomes phosphorylated in the presence of oestradiol (E2) as well as in the presence of the anti-oestrogens 4-hydroxytamoxifen (OHT) and ICI 164, 384 (ICI), although at lower efficiencies than with E2. There are multiple sites of phosphorylation in hER; using deletion and point mutants one of these sites has been mapped in the N-terminal A/B region at serine 118. Mutation of this serine to alanine caused, in a number of cell types, a significant reduction in transcriptional activation by hER from reporter genes containing an oestrogen response element (ERE), but did not affect the DNA binding properties or nuclear localization of hER. Thus phosphorylation of serine 118 is important for the action of the transcription activation function 1 (AF-1) located in the A/B region of the oestrogen receptor.
引用
收藏
页码:1153 / 1160
页数:8
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