Proteasomes are large multicatalytic complexes endowed with proteinase activity, located both in the cytosol and in the nucleus of eukaryotic cells. The ubiquitin–proteasome system is responsible for selective degradation of most intracellular proteins and therefore plays an essential regulatory role in many critical cellular processes. The proteasomal activity can also contribute to the pathological states of many diseases, including inflammation, neurodegeneration and cancer, through a disregulation in the level of regulatory proteins. These diseases may be targeted by modulating components of the ubiquitin–proteasome pathway, using small molecules as inhibitors. Bortezomib (Velcade®), used for the treatment of relapsed multiple myeloma, is the first and, up to now, the only proteasome inhibitor approved by the US FDA. Nowadays, the discovery that some metal-based complexes exert their antiproliferative action by affecting proteasomal activities provides the possibility of developing new opportunities in cancer therapy..

Targeting the ubiquitin-proteasome pathway with inorganic compounds to fight cancer: a challenge for the future

NARDON, CHIARA;
2012-01-01

Abstract

Proteasomes are large multicatalytic complexes endowed with proteinase activity, located both in the cytosol and in the nucleus of eukaryotic cells. The ubiquitin–proteasome system is responsible for selective degradation of most intracellular proteins and therefore plays an essential regulatory role in many critical cellular processes. The proteasomal activity can also contribute to the pathological states of many diseases, including inflammation, neurodegeneration and cancer, through a disregulation in the level of regulatory proteins. These diseases may be targeted by modulating components of the ubiquitin–proteasome pathway, using small molecules as inhibitors. Bortezomib (Velcade®), used for the treatment of relapsed multiple myeloma, is the first and, up to now, the only proteasome inhibitor approved by the US FDA. Nowadays, the discovery that some metal-based complexes exert their antiproliferative action by affecting proteasomal activities provides the possibility of developing new opportunities in cancer therapy..
ubiquitin–proteasome system
Bortezomib
Metal complexes
File in questo prodotto:
File Dimensione Formato  
Fregona.pdf

non disponibili

Dimensione 4.08 MB
Formato Adobe PDF
4.08 MB 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/11562/1062938
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 50
  • ???jsp.display-item.citation.isi??? 50
social impact