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-1α accumulation, or Hsp60-induced cell proliferation, are discussed along with strategies that might prove effective for developing Hsp60-targeting drugs for anticancer therapy.

Pace, A., Barone, G., Lauria, A., Martorana, A., Piccionello, A., Pierro, P., et al. (2013). Hsp60, a novel target for antitumor therapy: Structure-function features and prospective drugs design. CURRENT PHARMACEUTICAL DESIGN, 19(15), 2757-2764 [10.2174/1381612811319150011].

Hsp60, a novel target for antitumor therapy: Structure-function features and prospective drugs design

PACE, Andrea;BARONE, Giampaolo;LAURIA, Antonino;MARTORANA, Annamaria;PIERRO, Paola;TERENZI, Alessio;ALMERICO, Anna Maria;BUSCEMI, Silvestre;CAMPANELLA, Claudia;ANGILERI, Francesca;CARINI, Francesco;ZUMMO, Giovanni;CAPPELLO, Francesco;
2013-01-01

Abstract

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-1α accumulation, or Hsp60-induced cell proliferation, are discussed along with strategies that might prove effective for developing Hsp60-targeting drugs for anticancer therapy.
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/06 - Chimica Organica
Settore CHIM/03 - Chimica Generale E Inorganica
Settore BIO/16 - Anatomia Umana
Pace, A., Barone, G., Lauria, A., Martorana, A., Piccionello, A., Pierro, P., et al. (2013). Hsp60, a novel target for antitumor therapy: Structure-function features and prospective drugs design. CURRENT PHARMACEUTICAL DESIGN, 19(15), 2757-2764 [10.2174/1381612811319150011].
File in questo prodotto:
File Dimensione Formato  
13-CPD2757.pdf

Solo gestori archvio

Dimensione 901.21 kB
Formato Adobe PDF
901.21 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/72860
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 50
  • ???jsp.display-item.citation.isi??? 53
social impact