A PDZ Protein MDA-9/Syntenin: As a Target for Cancer Therapy

A PDZ Protein MDA-9/Syntenin: As a Target for Cancer Therapy
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PDZ 蛋白 MDA-9/Syntenin:作为癌症治疗的靶点

DOI:
10.1016/j.csbj.2019.01.002
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发表时间:
2019-01
期刊:
Comput Struct Biotechnol J
影响因子:
--
通讯作者:
Wan Xiaoping
Wan Xiaoping
中科院分区:
其他
文献类型:
--
作者:
Yu Yongsheng;Li Shuangdi;Wang Kai;Wan Xiaoping

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黑色素瘤分化相关基因 9 (MDA-9)/Syntenin 是一种多域 PDZ 蛋白,最初被确定为黑色素瘤的关键癌基因。该蛋白包含独特的串联 PDZ 结构域结构(PDZ1 和 PDZ2 由 4 个氨基酸接头间隔)、结构未表征的 N 端结构域 (NTD) 和短的 C 端结构域 (CTD)。 PDZ1 结构域被视为 PDZ 信号传导结构域,而 PDZ2 则被视为 PDZ 超家族结构域。它通过调节多种癌症类型中的许多主要信号传导途径而具有多种细胞作用。通过使用新的药物设计方法,例如我们组中抑制剂的二聚化和非天然氨基酸取代,该蛋白质可能提供有价值的治疗靶点。本综述的目的是提供关于 MDA-9/Syntenin 的癌症特异性作用的最新观点,以探索其在癌症药物发现和癌症治疗方面的潜力。
Melanoma differentiation-associated gene 9 (MDA-9)/Syntenin is a multidomain PDZ protein and identified as a key oncogene in melanoma initially. This protein contains a unique tandem PDZ domain architecture (PDZ1 and PDZ2 spaced by a 4-amino acid linker), an N-terminal domain (NTD) that is structurally uncharacterized and a short C-terminal domain (CTD). The PDZ1 domain is regarded as the PDZ signaling domain while PDZ2 served as the PDZ superfamily domain. It has various cellular roles by regulating many of major signaling pathways in numerous cancertypes. Through the use of novel drug design methods, such as dimerization and unnatural amino acid substitution of inhibitors in our group, the protein may provide a valuable therapeutic target. The objective of this review is to provide a current perspective on the cancer-specific role of MDA-9/Syntenin in order to explore its potential for cancer drug discovery and cancer therapy.
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