Document Detail


Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy.
MedLine Citation:
PMID:  21375465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase involved in regulation of the cell cycle through ubiquitination-dependent substrate proteolysis. Many viral proteins have been shown to interact with the APC/C, derailing cell cycle progression in order to facilitate their own replication. Induction of G(2)/M arrest by viral APC/C inhibition can lead to apoptotic cell death. Some viral proteins cause cytotoxicity specifically in tumour cells, providing evidence that targeting the APC/C could be exploited to selectively eliminate cancer cells.
AREAS COVERED: In this review, we provide a summary of studies from viral APC/C interactions over the last decade, as well as recent discoveries identifying the APC/C as a promising target in the context of cancer therapy.
EXPERT OPINION: Current therapeutic strategies inducing mitotic arrest rely on activation of the spindle assembly checkpoint (SAC) for their function. Many cancer cells have a weakened SAC and escape apoptosis through mitotic slippage. Recent evidence has demonstrated that targeting the APC/C, particularly the co-activator Cdc20, might be a better alternative. Tumour cells display greater dependency on APC/C function than normal cells and oncogenic transformation can lead to increased mitotic stress, rendering cancer cells more vulnerable to APC/C inhibition.
Authors:
Linda Smolders; Jose G Teodoro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2011-03-05
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  15     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-11     Completed Date:  2011-09-01     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  767-80     Citation Subset:  IM    
Affiliation:
McGill University, Goodman Cancer Research Centre, Department of Biochemistry, 1160 Pine Avenue West, Room 616, Montreal, Quebec H3A 1A3, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Apoptosis
Cell Cycle
Drug Delivery Systems*
Humans
Neoplasms / drug therapy,  physiopathology
Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors,  metabolism*
Viral Proteins / metabolism
Virus Diseases / drug therapy,  virology
Grant Support
ID/Acronym/Agency:
MOP-179122//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Viral Proteins; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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