Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family
Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family
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DOI：
10.1093/emboj/19.10.2292
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发表时间：
2000-05-15
期刊：
影响因子：
11.4
通讯作者：
Busslinger, M
中科院分区：
文献类型：
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作者：
Eberhard, D;Jiménez, G;Busslinger, M
Pax 5（BSAP）在中脑模式形成、B细胞发育和淋巴瘤发生过程中作为转录激活因子和抑制因子发挥作用。在这里，我们表明，Pax 5发挥其抑制功能，通过招募成员的Groucho corepressor家庭。在酵母双杂交筛选中，groucho相关基因产物Grg 4被鉴定为PaxS伴侣蛋白。这两种蛋白通过两个独立的结构域相互作用：Grg 4的N-末端Q和中央SP区，以及PaxS的八肽基序和C-末端反式激活结构域。在Pax 5结合后，Grg 4的磷酸化状态在体内改变。此外，Grg 4以八肽依赖的方式有效地抑制PaxS的转录活性。在Pax 2/5/8和Groucho蛋白家族的远亲成员之间观察到导致转录抑制的类似蛋白质相互作用。Pax蛋白的八肽基序在果蝇胚胎中起着Groucho依赖的阻遏结构域的作用，这些数据表明Pax蛋白可以通过与Groucho蛋白家族的辅阻遏物相互作用而从转录激活物转化为阻遏物。
Pax5 (BSAP) functions as both a transcriptional activator and repressor during midbrain patterning, B-cell development and lymphomagenesis. Here we demonstrate that Pax5 exerts its repression function by recruiting members of the Groucho corepressor family. In a yeast two-hybrid screen, the groucho-related gene product Grg4 was identified as a PaxS partner protein. Both proteins interact cooperatively via two separate domains: the N-terminal Q and central SP regions of Grg4, and the octapeptide motif and C-terminal transactivation domain of PaxS. The phosphorylation state of Grg4 is altered in vivo upon Pax5 binding. Moreover, Grg4 efficiently represses the transcriptional activity of PaxS in an octapeptide-dependent manner. Similar protein interactions resulting in transcriptional repression were observed between distantly related members of both the Pax2/5/8 and Groucho protein families. In agreement with this evolutionary conservation, the octapeptide motif of Pax proteins functions as a Groucho-dependent repression domain in Drosophila embryos, These data indicate that Pax proteins can be converted from transcriptional activators to repressors through interaction with corepressors of the Groucho protein family.