The critical protein interactions and structures that elicit growth deregulation in cancer and viral replication
- 15 April 2010
- journal article
- review article
- Published by Wiley in Wires Systems Biology and Medicine
- Vol. 3 (1), 48-73
- https://doi.org/10.1002/wsbm.88
Abstract
One of the greatest challenges in biomedicine is to define the critical targets and network interactions that are subverted to elicit growth deregulation in human cells. Understanding and developing rational treatments for cancer requires a definition of the key molecular targets and how they interact to elicit the complex growth deregulation phenotype. Viral proteins provide discerning and powerful probes to understand both how cells work and how they can be manipulated using a minimal number of components. The small DNA viruses have evolved to target inherent weaknesses in cellular protein interaction networks to hijack the cellular DNA and protein replication machinery. In the battle to escape the inevitability of senescence and programmed cell death, cancers have converged on similar mechanisms, through the acquisition and selection of somatic mutations that drive unchecked cellular replication in tumors. Understanding the dynamic mechanisms through which a minimal number of viral proteins promote host cells to undergo unscheduled and pathological replication is a powerful strategy to identify critical targets that are also disrupted in cancer. Viruses can therefore be used as tools to probe the system‐wide protein‐protein interactions and structures that drive growth deregulation in human cells. Ultimately this can provide a path for developing system context‐dependent therapeutics. This review will describe ongoing experimental approaches using viruses to study pathways deregulated in cancer, with a particular focus on viral cellular protein‐protein interactions and structures. WIREs Syst Biol Med 2011 3 48–73 DOI: 10.1002/wsbm.88 This article is categorized under: Developmental Biology > Developmental Processes in Health and DiseaseKeywords
This publication has 148 references indexed in Scilit:
- The cancer genomeNature, 2009
- Direct association of the HPV16 E7 oncoprotein with cyclin A/CDK2 and cyclin E/CDK2 complexesVirology, 2008
- Patterns of somatic mutation in human cancer genomesNature, 2007
- The Epigenomics of CancerCell, 2007
- Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeastMolecular Systems Biology, 2007
- Finishing the euchromatic sequence of the human genomeNature, 2004
- Network biology: understanding the cell's functional organizationNature Reviews Genetics, 2004
- Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compoundNature Medicine, 2002
- Functional organization of the yeast proteome by systematic analysis of protein complexesNature, 2002
- The Hallmarks of CancerCell, 2000