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J Clin Oncol ; 31(9): 1231-8, 2013 Mar 20.
Article in English | MEDLINE | ID: mdl-23358974

ABSTRACT

The ubiquitin proteasome system (UPS) regulates the ubiquitination, and thus degradation and turnover, of many proteins vital to cellular regulation and function. The UPS comprises a sequential series of enzymatic processes using four key enzyme families: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-carrier proteins), E3 (ubiquitin-protein ligases), and E4 (ubiquitin chain assembly factors). Because the UPS is a crucial regulator of the cell cycle, and abnormal cell-cycle control can lead to oncogenesis, aberrancies within the UPS pathway can result in a malignant cellular phenotype and thus has become an attractive target for novel anticancer agents. This article will provide an overall review of the mechanics of the UPS, describe aberrancies leading to cancer, and give an overview of current drug therapies selectively targeting the UPS.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Transformation, Neoplastic , Proteasome Endopeptidase Complex/physiology , Ubiquitin-Activating Enzymes/physiology , Ubiquitin-Conjugating Enzymes/physiology , Ubiquitin-Protein Ligases/physiology , Antineoplastic Agents/therapeutic use , Cyclin-Dependent Kinase Inhibitor p27/physiology , DNA-Binding Proteins/physiology , Humans , Male , Mutation , Oncogene Proteins, Viral/physiology , Prostatic Neoplasms/genetics , Proteasome Endopeptidase Complex/drug effects , Proto-Oncogene Proteins c-mdm2/physiology , Tumor Suppressor Protein p53/physiology , Ubiquitin-Protein Ligases/antagonists & inhibitors , Ubiquitin-Protein Ligases/genetics
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