Rajaiya Jaya, Nixon Jamee C, Ayers Neil, Desgranges Zana P, Roy Ananda L, Webb Carol F
Oklahoma Medical Research Foundation, Immunobiology and Cancer Research Program, 825 N. E. 13th Street, Oklahoma City, OK 73104, USA.
Mol Cell Biol. 2006 Jun;26(12):4758-68. doi: 10.1128/MCB.02009-05.
Bright/ARID3a/Dril1, a member of the ARID family of transcription factors, is expressed in a highly regulated fashion in B lymphocytes, where it enhances immunoglobulin transcription three- to sixfold. Recent publications from our lab indicated that functional, but not kinase-inactive, Bruton's tyrosine kinase (Btk) is critical for Bright activity in an in vitro model system, yet Bright itself is not appreciably tyrosine phosphorylated. These data suggested that a third protein, and Btk substrate, must contribute to Bright-enhanced immunoglobulin transcription. The ubiquitously expressed transcription factor TFII-I was identified as a substrate for Btk several years ago. In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels. These data suggest that Bright functions as a three-component protein complex in the immunoglobulin locus and tie together previous data indicating important roles for Btk and TFII-I in B lymphocytes.
Bright/ARID3a/Dril1是转录因子ARID家族的成员之一，在B淋巴细胞中以高度调控的方式表达，可使免疫球蛋白转录增强三到六倍。我们实验室最近发表的文章表明，在体外模型系统中，具有功能活性而非激酶失活的布鲁顿酪氨酸激酶（Btk）对Bright的活性至关重要，然而Bright本身并没有明显的酪氨酸磷酸化。这些数据表明，必定存在第三种蛋白质作为Btk的底物，它有助于Bright增强免疫球蛋白转录。几年前，普遍表达的转录因子TFII-I被鉴定为Btk的底物。在这项研究中，我们发现TFII-I通过Bright蛋白相互作用结构域中的氨基酸与人Bright直接相互作用，并且TFII-I的特定酪氨酸残基对于Bright诱导的免疫球蛋白报告基因活性至关重要。此外，在B细胞系中抑制TFII-I的功能会导致重链转录水平降低。这些数据表明，Bright在免疫球蛋白基因座中作为一种三元蛋白质复合物发挥作用，并将先前表明Btk和TFII-I在B淋巴细胞中起重要作用的数据联系在一起。
