The transcriptional repressor protein PRH interacts with the proteasome
The transcriptional repressor protein PRH interacts with the proteasome
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DOI：
10.1042/bj20030769
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发表时间：
2003-09-14
影响因子：
4.1
通讯作者：
Jayaraman, PS
中科院分区：
文献类型：
--
作者：
Bess, KL;Swingler, TE;Jayaraman, PS
PRH（proline-rich homeodomain protein，富含脯氨酸的同源结构域蛋白）/Hex在控制细胞增殖和分化中是重要的。我们以前已经表明，PRH包含两个域，可以独立地带来转录抑制; PRH同源结构域抑制转录通过结合TATA盒序列，而脯氨酸丰富的N-末端结构域可以抑制转录通过与成员的Groucho/TLE（transformin-like enhancer of split）家族的共阻遏蛋白。蛋白酶体是参与蛋白质加工和降解的多亚基蛋白质复合物。一些蛋白酶体亚基被认为在转录调控中起作用。在本研究中，我们表明，PRH与HC 8亚基的蛋白酶体的上下文中的20和26 S蛋白酶体相互作用。此外，我们表明，PRH与造血细胞中的蛋白酶体和富含脯氨酸的PRH N-末端结构域是负责这种相互作用。尽管PRH可以被蛋白酶体切割，但它似乎在体外或体内都不会迅速降解，并且蛋白酶体的蛋白水解活性对于PRH的转录抑制是不需要的。然而，PRH的蛋白酶体消化可以释放保留与DNA结合的能力的截短的PRH蛋白。我们讨论这些发现的生物学作用的PRH基因调控和细胞增殖的控制。
PRH (proline-rich homeodomain protein)/Hex is important in the control of cell proliferation and differentiation. We have shown previously that PRH contains two domains that can bring about transcriptional repression independently; the PRH homeodomain represses transcription by binding to TATA box sequences, whereas the proline-rich N-terminal domain can repress transcription by interacting with members of the Groucho/TLE (transducin-like enhancer of split) family of co-repressor proteins. The proteasome is a multi-subunit protein complex involved in the processing and degradation of proteins. Some proteasome subunits have been suggested to play a role in the regulation of transcription. In the present study, we show that PRH interacts with the HC8 subunit of the proteasome in the context of both 20 and 26 S proteasomes. Moreover, we show that PRH is associated with the proteasome in haematopoietic cells and that the proline-rich PRH N-terminal domain is responsible for this interaction. Whereas PRH can be cleaved by the proteasome, it does not appear to be degraded rapidly in vitro or in vivo, and the proteolytic activity of the proteasome is not required for transcriptional repression by PRH. However, proteasomal digestion of PRH can liberate truncated PRH proteins that retain the ability to bind to DNA. We discuss these findings in terms of the biological role of PRH in gene regulation and the control of cell proliferation.