Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion.
Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion.
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DOI：
10.1186/s13578-016-0077-7
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发表时间：
2016
影响因子：
7.5
通讯作者：
Jayaraman PS
中科院分区：
文献类型：
--
作者：
Gaston K;Tsitsilianos MA;Wadey K;Jayaraman PS
脯氨酸富同源结构域蛋白（PRH），也被称为造血表达同源盒（HHEX），是胚胎发育和成人发育过程中必不可少的转录因子。PRH蛋白形成寡聚复合物，与PRH靶基因内或靶基因附近的串联重复的PRH识别序列结合，并招募多种PRH相互作用蛋白。PRH也可以与其他转录因子结合，直接通过DNA结合或间接通过影响其伴侣蛋白的活性来共同调节特定的靶基因。此外，与其他同源结构域蛋白一样，PRH可以调节特定mrna的翻译。PRH表达的改变和PRH细胞内定位的改变与乳腺癌、肝癌、甲状腺癌和某些亚型白血病有关。这与多种prh相互作用蛋白的参与一致，包括癌蛋白c-Myc、翻译起始因子4E （eIF4E）和早幼粒细胞白血病蛋白（PML），在细胞增殖和细胞存活的控制中。同样，多种PRH靶基因，包括编码血管内皮生长因子（VEGF）、VEGF受体、内啡肽和Goosecoid的基因，已知在控制细胞增殖和细胞存活和/或调节细胞迁移和侵袭方面发挥重要作用。在这篇综述中，我们总结了PRH参与肿瘤发生的证据，并回顾了PRH水平可能对癌症预后和治疗方案选择有用的数据。
The proline rich homeodomain protein (PRH), also known as haematopoietically expressed homeobox (HHEX), is an essential transcription factor in embryonic development and in the adult. The PRH protein forms oligomeric complexes that bind to tandemly repeated PRH recognition sequences within or at a distance from PRH-target genes and recruit a variety of PRH-interacting proteins. PRH can also bind to other transcription factors and co-regulate specific target genes either directly through DNA binding, or indirectly through effects on the activity of its partner proteins. In addition, like some other homeodomain proteins, PRH can regulate the translation of specific mRNAs. Altered PRH expression and altered PRH intracellular localisation, are associated with breast cancer, liver cancer and thyroid cancer and some subtypes of leukaemia. This is consistent with the involvement of multiple PRH-interacting proteins, including the oncoprotein c-Myc, translation initiation factor 4E (eIF4E), and the promyelocytic leukaemia protein (PML), in the control of cell proliferation and cell survival. Similarly, multiple PRH target genes, including the genes encoding vascular endothelial growth factor (VEGF), VEGF receptors, Endoglin, and Goosecoid, are known to be important in the control of cell proliferation and cell survival and/or the regulation of cell migration and invasion. In this review, we summarise the evidence that implicates PRH in tumourigenesis and we review the data that suggests PRH levels could be useful in cancer prognosis and in the choice of treatment options.
影响因子：
14.9
作者：
Soufi A;Sawasdichai A;Shukla A;Noy P;Dafforn T;Smith C;Jayaraman PS;Gaston K
通讯作者：
Gaston K