Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression

被引:88
作者
Engblom, David
Kornfeld, Jan-Wilhelm
Schwake, Lukas
Tronche, Francois
Reimann, Andreas
Beug, Hartmut
Hennighausen, Lothar
Moriggl, Richard [1 ]
Schuetz, Guenther
机构
[1] German Canc Res Ctr, Div Mol Biol Cell 1, D-69120 Heidelberg, Germany
[2] Ludwig Boltzmann Inst Canc Res, A-1090 Vienna, Austria
[3] CNRS, Coll France, UMR 7148, F-75231 Paris, France
[4] CNRS, Dept Dev Biol, Pasteur FRE 2850, F-75014 Paris, France
[5] Inst Mol Pathol, A-1030 Vienna, Austria
[6] NIDDKD, NIH, Bethesda, MD 20892 USA
关键词
somatomedin; liver; Cre-loxP; growth hormone; microarray; GROWTH-FACTOR-I; DNA-BINDING; LYMPHOID DEVELOPMENT; SIGNAL TRANSDUCER; BONE-GROWTH; STAT5; TRANSCRIPTION; DIFFERENTIATION; REPRESSION; ACTIVATOR;
D O I
10.1101/gad.426007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The glucocorticoid receptor regulates transcription through DNA binding as well as through cross-talk with other transcription factors. In hepatocytes, the glucocorticoid receptor is critical for normal postnatal growth. Using hepatocyte- specific and domain-selective mutations in the mouse we show that Stat5 in hepatocytes is essential for normal postnatal growth and that it mediates the growth- promoting effect of the glucocorticoid receptor through a direct interaction involving the N-terminal tetramerization domain of Stat5b. This interaction mediates a selective and unexpectedly extensive part of the transcriptional actions of these molecules since it controls the expression of gene sets involved in growth and sexual maturation.
引用
收藏
页码:1157 / 1162
页数:6
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