Ptx1 regulates SF‐1 activity by an interaction that mimics the role of the ligand‐binding domain
Ptx1 regulates SF‐1 activity by an interaction that mimics the role of the ligand‐binding domain
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DOI：
10.1093/emboj/18.12.3431
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发表时间：
1999-06
期刊：
影响因子：
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通讯作者：
J. Tremblay;Alexandre Marcil;Yves Gauthier;J. Drouin
中科院分区：
文献类型：
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作者：
J. Tremblay;Alexandre Marcil;Yves Gauthier;J. Drouin
Ptx1 (Pitx1) 是一种双类相关同源盒转录因子，在垂体发育开始时表达。它被证明与细胞限制因子，如 Pit1、NeuroD1/PanI 和类固醇生成因子 1 (SF-1) 合作，建立一个组合密码，赋予垂体中谱系和启动子特异性基因转录。 Ptx1 和 SF-1 在两个 SF-1 靶基因（垂体黄体生成素 β 和苗勒管抑制物质 (MIS)）上的转录协同作用需要 SF-1 与 DNA 结合，并且似乎是这两种蛋白质之间直接物理相互作用的结果。 Ptx1 的 C 端和 SF-1 的 N 端一半之间的相互作用导致转录增强，其活性相当于组成型活性 SF-1 突变体的活性，并且可能模拟尚未鉴定的 SF-1 配体的作用。因此，Ptx1 揭示 SF-1 活性可能代表了一种发育机制，可减轻转录中以及可能在器官发生过程中关键时刻对 SF-1 配体的需求。
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 β and Müllerian‐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 may represent a developmental mechanism to alleviate the need for SF‐1 ligand in transcription and, possibly, at critical times during organogenesis.