Ptx1 regulates SF-1 activity by an interaction that mimics the role of the ligand-binding domain

被引:104
作者
Tremblay, JJ [1 ]
Marcil, A [1 ]
Gauthier, Y [1 ]
Drouin, J [1 ]
机构
[1] Inst Rech Clin Montreal, Genet Mol Lab, Montreal, PQ H2W 1R7, Canada
关键词
cofactor; homeobox; ligand; nuclear receptors; Pitx;
D O I
10.1093/emboj/18.12.3431
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
Ptx1 (Pitx1) is a bicoid-related homeobox transcription factor expressed from the onset of pituitary development. It was shown to cooperate with cell-restricted factors, such as Pit1, NeuroD1/PanI and steroidogenic factor 1 (SF-1), to establish a combinatorial code conferring lineage- and promoter-specific gene transcription in the pituitary. Transcriptional synergism between Ptx1 and SF-1 on two SF-1 target genes, pituitary luteinizing hormone beta and Mullerian-inhibiting substance (MIS), requires SF-1 binding to DNA and appears to result from direct physical interaction between these two proteins. The interaction between the C-terminus of Ptx1 and the N-terminal half of SF-1 results in transcriptional enhancement that equals the activity of a constitutively active SF-1 mutant and that may mimic the effect of a still unidentified SF-1 ligand. Thus, the unmasking of SF-1 activity by Ptx1 mag represent a developmental mechanism to alleviate the need for SF-1 ligand in transcription and, possibly, at critical times during organogenesis.
引用
收藏
页码:3431 / 3441
页数:11
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