A new Groucho TLE4 protein may regulate the repressive activity of Pax5 in human B lymphocytes
A new Groucho TLE4 protein may regulate the repressive activity of Pax5 in human B lymphocytes
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DOI：
10.1046/j.1365-2567.2002.01456.x
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发表时间：
2002-08-01
期刊：
影响因子：
6.4
通讯作者：
Schiff, C
中科院分区：
文献类型：
--
作者：
Milili, M;Gauthier, L;Schiff, C
在小鼠B细胞发育过程中，Pax5是一种基本的转录因子，它作为B细胞特异性基因的激活因子，并作为另一种血统命运的抑制因子。这种抑制作用是通过招募Groucho共抑制因子家族的成员来实现的。使用RNA展示方法，我们已经分离出一种称为QD的转录本，它专门在人类Pro-B和Pre-B细胞中表达，它来自人类Groucho TLE4基因。QD转录本包含TLE4的前4个外显子和外显子4的内含子序列3‘，表明QD是TLE4的剪接变体。推测得到的94个氨基酸的蛋白质对应于大约一半的N-末端四聚结构域。我们还显示了TLE4转录本在人类B细胞中的特异性表达以及TLE4蛋白在B细胞核中的特异性表达。此外，我们还证明了重组QD蛋白能与TLE4的Q结构域结合，并能取消TLE4/Pax5的相互作用。因此，在B细胞分化早期，QD可能是TLE4功能的负调控因子。
During mouse B-cell development, Pax5 is an essential transcription factor that acts as an activator of B-cell-specific genes and as a repressor of alternative lineage fates. The repressive function is mediated by the recruitment of members of the Groucho co-repressor family. Using an RNA display approach, we have isolated a transcript, called QD, specifically expressed in human pro-B and pre-B cells, which is derived from the human Groucho TLE4 gene. The QD transcript contains the first four TLE4 exons and an intronic sequence 3' of exon 4, demonstrating that QD is a splice variant of TLE4. The putative resulting protein of 94 amino acids corresponds to approximately half of an N-terminal tetramerization domain. We also show specific expression of TLE4 transcripts in human B cells and of TLE4 proteins in B-cell nuclei. Moreover, we demonstrate that recombinant QD protein binds to the TLE4 Q domain and is able to abolish the TLE4/Pax5 interaction. Thus, QD could act as a negative regulator of TLE4 function, in early B-cell differentiation.