Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors
Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors
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DOI：
10.1074/jbc.275.18.13336
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发表时间：
2000-05-05
影响因子：
4.8
通讯作者：
Maurer, RA
中科院分区：
文献类型：
--
作者：
Howard, PW;Maurer, RA
Lhx3是LIM同源结构域转录因子家族中的一员，是垂体发育所必需的，参与了垂体特异性激素基因的转录。在这份报告中，我们描述了一种新的基因产物SLB，它选择性地与Lhx3和密切相关的LIM因子Lhx4相互作用。SLB基因编码一个1749个残基的蛋白质，在氨基端附近有7个WD40重复序列和一个可能的核定位信号，不包含其他可识别的基序。SLB以组织特异性的方式表达，在睾丸和垂体细胞中SLB mRNA的表达浓度最高。我们证明SLB在体外和体内都能与Lhx3和Lhx4高亲和力结合。SLB与其他LIM结构域的亲和力较低或检测不到亲和力，含有LIM相互作用结构域的SLB片段的表达载体可减少Lhx3反应报告基因的表达。SLB的LIM相互作用结构域改变报告基因活性的能力以及SLB与LIM因子结合的组织特异性表达和特异性表明，SLB可能在调节特定LIM因子的转录活性中发挥作用。
Lhx3, a member of the LIM homeodomain family of transcription factors, is required for development of the pituitary and is implicated in the transcription of pituitary-specific hormone genes. In this report we describe a novel gene product, SLB, that selectively interacts with Lhx3 and the closely related LIM factor, Lhx4. The SLB cDNA encodes a 1749-residue protein that contains seven WD40 repeats near the amino terminus and a putative nuclear localization signal and does not contain other recognizable motifs. SLB is expressed in a tissue-specific manner with the highest concentrations of SLB mRNA in the testis and pituitary cells. We demonstrate that SLB specifically binds to Lhx3 and Lhx4 with high affinity both in vitro and in vivo. SLB has much lower affinity or no detectable affinity for other LIM domains, An expression vector for a fragment of SLB containing the LIM-interaction domain was shown to reduce expression of Lhx3-responsive reporter genes. The ability of the LIM-interacting domain of SLB to alter reporter gene activity as well as the tissue-specific expression and the specificity of SLB binding to LIM factors suggest a possible role in modulating the transcriptional activity of specific LIM factors.