Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Ubiquitylation and Cancer Development

Author(s): John Silke, Maria Miasari and Hamsa Puthalakath

Volume 8, Issue 2, 2008

Page: [118 - 123] Pages: 6

DOI: 10.2174/156800908783769300

Price: $65

Abstract

Ubiquitylation is an essential cellular process, and yet many cancer cells appear to be more reliant upon it than normal cells as they are surprisingly sensitive to proteasome inhibitors (PI) and proteasome inhibitor drugs are well tolerated in vivo. Several reviews have suggested that specific protein targets account for PI induced cell death, but fail to adequately explain why cancer cells are more sensitive than normal cells to PIs. We review the evidence for these models, focusing primarily on inducers of cell death including p53 and the pro-apoptotic Bcl-2 Homology proteins (BH3 proteins) and propose an additional hypothesis; that a tumour cells abnormal physiology makes it particularly reliant upon the proteasome. This hypothesis is well supported in the case of Multiple Myelomas, that may produce large amounts of antibodies and are therefore under considerable ER strain and in turn particularly reliant upon the proteasome to clear the large numbers of misfolded proteins. We propose that other cell types, tumor or non tumour, that are already under ER stress, or its equivalent, maybe particularly susceptible to proteasome inhibitors.


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy