Hsp60, a Novel Target for Antitumor Therapy: Structure-Function Features and Prospective Drugs Design

作者：Pace Andrea; Barone Giampaolo; Lauria Antonino; Martorana Annamaria; Piccionello Antonio Palumbo; Pierro Paola; Terenzi Alessio; Almerico Anna Maria; Buscemi Silvestre; Campanella Claudia; Angileri Francesca; Carini Francesco; Zummo Giovanni; de Macario Everly Conway; Cappello Francesco^*; Macario Alberto J L

来源：Current Pharmaceutical Design, 2013, 19(15): 2757-2764.

DOI：10.2174/1381612811319150011

• Hsp60
• chaperonin
• functional domains
• binding pocket
• compound docking
• epolactaene
• drug design
• cancer treatment

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%26apos;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.

• 出版日期2013-5