Ets-related protein PU.1 regulates expression of the immunoglobulin J-chain gene through a novel Ets-binding element.
Ets-related protein PU.1 regulates expression of the immunoglobulin J-chain gene through a novel Ets-binding element.
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Ets 相关蛋白 PU.1 通过新型 Ets 结合元件调节免疫球蛋白 J 链基因的表达。
DOI：
10.1101/gad.7.10.2006
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发表时间：
1993
影响因子：
10.5
通讯作者：
Koshland,ME
中科院分区：
文献类型：
--
作者：
Shin,MK;Koshland,ME
在初次免疫应答中，来自白细胞介素-2（IL-2）的信号激活编码五聚体IgM连接组分（J链）的基因的转录。最近，J链启动子中的双功能控制元件（JB）已被鉴定。在本研究中，通过纯化和表征介导JB元件的正调控活性的核蛋白（NF-JB）来追求这一发现。分析表明，NF-JB是相同的Ets相关的B细胞和巨噬细胞特异性转录因子，PU.1，尽管事实上，JB网站缺乏GGA核心报告是必不可少的结合Ets癌蛋白家族的成员。这两个因素被认为是不可区分的，就其DNA结合特性，大小和肽结构。此外，在瞬时转染试验中，PU.1单独激活含有JB顺式元件的报告构建体，并且该激活显示依赖于PU.1的氨基末端部分中的富含谷氨酰胺的序列。最后，一个显性负突变的PU.1是能够抑制1.2 kb的J链启动子序列的转录活性。这些结果确立了PU.1在免疫球蛋白J链基因表达调控中的重要作用，并为淋巴细胞中Ets转录因子的功能提供了新的见解。
In a primary immune response, a signal from interleukin-2 (IL-2) activates transcription of the gene encoding the pentamer IgM joining component, the J chain. Recently, a bifunctional control element (JB) in the J-chain promoter has been identified. This finding was pursued in the present study by purifying and characterizing the nuclear protein (NF-JB) that mediates the positive regulatory activity of the JB element. The analyses revealed that NF-JB is identical to the Ets-related B-cell- and macrophage-specific transcriptional factor, PU.1, despite the fact that the JB site lacks the GGA core reported to be essential for binding by members of the Ets oncoprotein family. The two factors were found to be indistinguishable with respect to their DNA-binding characteristics, size, and peptide structure. Moreover, in transient transfection assays, PU.1 alone activated reporter constructs containing the JB cis-element, and the activation was shown to be dependent on a glutamine-rich sequence in the amino-terminal portion of PU.1. Finally, a dominant negative mutant of PU.1 was capable of suppressing the transcriptional activity of a 1.2-kb J-chain promoter sequence. These results establish an important role for PU.1 in the regulation of immunoglobulin J-chain gene expression and provide new insights into the function(s) of the Ets transcription factors in lymphoid cells.