Hsp60, a Novel Target for Antitumor Therapy: Structure-Function Features and Prospective Drugs Design
Hsp60, a Novel Target for Antitumor Therapy: Structure-Function Features and Prospective Drugs Design
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DOI：
10.2174/1381612811319150011
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Macario, Alberto J. L.
中科院分区：
文献类型：
--
作者：
Pace, Andrea;Barone, Giampaolo;Macario, Alberto J. L.
热休克蛋白60 kDa（Hsp 60）是一种分子伴侣，被认为参与帮助其他线粒体蛋白的正确折叠。Hsp 60还在针对细胞应激物的细胞保护中起作用，例如显示抗凋亡潜力。尽管有大量的研究致力于Hsp 60的功能机制，特别是在原核生物中，但基本问题仍然未被探索，包括其在癌症中的作用的定义。关键的问题仍然没有答案属于结构-功能特征的差异，可能存在于研究充分的原核GroEL和大部分未开发的真核Hsp 60蛋白之间。在这篇文章中，我们讨论了这些差异的序列，结构和作用的热休克蛋白60，专注于人类直系同源物的观点，设计的化合物，以阻止其能力，有利于肿瘤细胞的生长和生存。化合物目前已知直接或间接影响Hsp 60的功能，如蛋白质折叠，HIF-1 α积累，或Hsp 60诱导的细胞增殖，讨论沿着的策略，可能证明有效的开发Hsp 60靶向药物的抗癌治疗。
Heat shock protein 60kDa (Hsp60) is a chaperone classically believed to be involved in assisting the correct folding of other mitochondrial proteins. Hsp60 also plays a role in cytoprotection against cell stressors, displaying for example, antiapoptotic potential. Despite the plethora of studies devoted to the mechanism of Hsp60's function, especially in prokaryotes, fundamental issues still remain unexplored, including the definition of its role in cancer. Key questions still unanswered pertain to the differences in structure-function features that might exist between the well-studied prokaryotic GroEL and the largely unexplored eukaryotic Hsp60 proteins. In this article we discuss these differences in sequence, structure, and roles of Hsp60, focusing on the human ortholog with the view of devising compounds to block its ability to favour tumor-cell growth and survival. Compounds currently known to directly or indirectly affect Hsp60 functions, such as protein folding, HIF-1 alpha accumulation, or Hsp60-induced cell proliferation, are discussed along with strategies that might prove effective for developing Hsp60-targeting drugs for anticancer therapy.