title: Hsp60, a novel target for antitumor therapy: structure-function features and prospective drugs design.
abstract: Heat shock protein 60 kDa (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-1α accumulation, or Hsp60-induced cell proliferation, are discussed along with strategies that might prove effective for developing Hsp60-targeting drugs for anticancer therapy.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO) - Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Barone
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
authors.forename: Annamaria
authors.initials: A
authors.lastname: Martorana
authors.forename: Antonio Palumbo
authors.initials: AP
authors.lastname: Piccionello
authors.forename: Paola
authors.initials: P
authors.lastname: Pierro
authors.forename: Alessio
authors.initials: A
authors.lastname: Terenzi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
authors.forename: Silvestre
authors.initials: S
authors.lastname: Buscemi
authors.forename: Claudia
authors.initials: C
authors.lastname: Campanella
authors.forename: Francesca
authors.initials: F
authors.lastname: Angileri
authors.forename: Francesco
authors.initials: F
authors.lastname: Carini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zummo
authors.forename: Everly Conway
authors.initials: EC
authors.lastname: de Macario
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.forename: Alberto J L
authors.initials: AJ
authors.lastname: Macario
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018834:Chaperonin 60 / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D018834:Chaperonin 60