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An insight into the complex roles of metallothioneins in malignant diseases with emphasis on (sub)isoforms/isoforms and epigenetics phenomena
Pharmacology & Therapeutics ( IF 13.5 ) Pub Date : 2017-10-05 , DOI: 10.1016/j.pharmthera.2017.10.004
Sona Krizkova , Marta Kepinska , Gabriella Emri , Tomas Eckschlager , Marie Stiborova , Petra Pokorna , Zbynek Heger , Vojtech Adam

Metallothioneins (MTs) belong to a group of small cysteine-rich proteins that are ubiquitous throughout all kingdoms. The main function of MTs is scavenging of free radicals and detoxification and homeostating of heavy metals. In humans, 16 genes localized on chromosome 16 have been identified to encode four MT isoforms labelled by numbers (MT-1–MT-4). MT-2, MT-3 and MT-4 proteins are encoded by a single gene. MT-1 comprises many (sub)isoforms. The known active MT-1 genes are MT-1A, -1B, -1E, -1F, -1G, -1H, -1M and -1X. The rest of the MT-1 genes (MT-1C, -1D, -1I, -1J and -1L) are pseudogenes. The expression and localization of individual MT (sub)isoforms and pseudogenes vary at intra-cellular level and in individual tissues. Changes in MT expression are associated with the process of carcinogenesis of various types of human malignancies, or with a more aggressive phenotype and therapeutic resistance. Hence, MT (sub)isoform profiling status could be utilized for diagnostics and therapy of tumour diseases. This review aims on a comprehensive summary of methods for analysis of MTs at (sub)isoforms levels, their expression in single tumour diseases and strategies how this knowledge can be utilized in anticancer therapy.



中文翻译:

深入了解金属硫蛋白在恶性疾病中的复杂作用,重点是(亚)同工型/同工型和表观遗传学现象

金属硫蛋白(MTs)属于一组富含半胱氨酸的小蛋白,在所有王国中普遍存在。MTs的主要功能是清除自由基,对重金属进行解毒和体内平衡。在人类中,已经确定了位于16号染色体上的16个基因编码了四个用数字标记的MT同工型(MT-1–MT-4)。MT-2,MT-3和MT-4蛋白由单个基因编码。MT-1包含许多(亚)同工型。已知的活性MT-1基因是MT-1A-1B-1E-1F-1G-1H-1M-1X。其余的MT-1基因(MT-1C-1D-1I-1J-1L)是假。单个MT(亚)亚型和假基因的表达和定位在细胞内水平和单个组织中有所不同。MT表达的变化与各种类型的人类恶性肿瘤的癌变过程有关,或者与更具攻击性的表型和治疗抗性有关。因此,MT(亚)同工型谱状态可以用于肿瘤疾病的诊断和治疗。这篇综述的目的是对(亚)同工型水平的MT的分析方法的全面总结,它们在单一肿瘤疾病中的表达以及如何在抗癌治疗中利用这些知识的策略。

更新日期:2017-10-05
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