Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects
Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects
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DOI：
10.5772/intechopen.70352
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发表时间：
2018-02
期刊：
影响因子：
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通讯作者：
Fumiaki Uchiumi
中科院分区：
文献类型：
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作者：
Fumiaki Uchiumi
控制细胞增殖和细胞迁移的调节机制的破坏会导致多种疾病状态，包括癌症和白血病。富含脯氨酸的同源异型域蛋白(PRH)/造血表达的同源异型盒蛋白(HHEX)是一种转录因子，在成体和胚胎的各种组织中控制细胞的增殖和迁移。蛋白激酶CK2(Casein Kinase II)使PRH磷酸化，阻止PRH与DNA结合并调控其直接靶基因的转录。在白血病细胞中，磷酸化也导致蛋白酶体产生一种跨显性负截短的PRH磷酸蛋白。PRH在乳腺和前列腺癌细胞中的磷酸化增加，随之而来的PRH活性的丧失增加了细胞的增殖和迁移。PRH还调节血管平滑肌细胞的增殖，在血管内膜增厚过程中，这些细胞中依赖CK2的PRH磷酸化伴随着细胞增殖的增加。因此，PRH调节细胞行为的能力和CK2控制PRH的能力并不局限于特定的细胞类型或组织。这增加了PRH-CK2轴在多种疾病状态中被作为靶点的可能性，从多发性癌症到静脉搭桥失败和再狭窄中发生的内膜增厚。
Disruption of the regulatory mechanisms that control cell proliferation and cell migration results in multiple disease states including cancer and leukemia. The Proline-Rich Homeodomain protein (PRH)/haematopoietically expressed homeobox protein (HHEX) is a transcription factor that controls cell proliferation and cell migration in a variety of tissues in the adult and in the embryo. Phosphorylation of PRH by Protein Kinase CK2 (Casein Kinase II) stops PRH from binding to DNA and regulating the transcription of its direct target genes. In leukaemic cells phosphorylation also results in the production of a transdominant-negative truncated PRH phosphoprotein by the proteasome. Phosphorylation of PRH is increased in breast and prostate cancer cells and the consequent loss of PRH activity increases cell proliferation and migration. PRH also regulates the proliferation of vascular smooth muscle cells and CK2-dependent phosphorylation of PRH in these cells accompanies increased cell proliferation during intimal thickening. Thus the ability of PRH to regulate cell behaviour and the control of PRH by CK2 is not limited to a specific cell type or tissue. This raises the possibility that the PRH-CK2 axis could be targeted in a variety of disease states ranging from multiple cancers to the intimal thickening that occurs in vein bypass graft failure and restenosis.