Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Ubiquitin in Cell-Cycle Regulation and Dysregulation in Cancer

Ubiquitin in Cell-Cycle Regulation and Dysregulation in Cancer Uncontrolled cell proliferation and genomic instability are common features of cancer and can arise from, respectively, the loss of cell-cycle control and defective checkpoints. Ubiquitin-mediated proteolysis, ultimately executed by ubiquitin-ligating enzymes (E3s), plays a key part in cell-cycle regulation and is dominated by two multisubunit E3s, the anaphase-promoting complex (or cyclosome) (APC/C) and SKP1–cullin-1–F-box (SCF) complex. We highlight the role of APC/C and the SCF bound to F-box proteins, FBXW7, SKP2, and β-TrCP, in regulating the abundance of select fundamental proteins, primarily during the cell cycle, that are associated with human cancer. The clinical success of the first proteasome inhibitor, bortezomib, in treating multiple myeloma and mantle-cell lymphoma set the precedent for viewing the ubiquitin–proteasome system as a druggable target for cancer. Given that there are more E3s than kinases, selective, small-molecule E3 inhibitors have the potential of opening up another dimension in the therapeutic armamentarium for the treatment of cancer. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Cancer Biology Annual Reviews

Ubiquitin in Cell-Cycle Regulation and Dysregulation in Cancer

Loading next page...
 
/lp/annual-reviews/ubiquitin-in-cell-cycle-regulation-and-dysregulation-in-cancer-upuVe9OV7N
Publisher
Annual Reviews
Copyright
Copyright © 2017 by Annual Reviews. All rights reserved
ISSN
2472-3428
eISSN
2472-3428
DOI
10.1146/annurev-cancerbio-040716-075607
Publisher site
See Article on Publisher Site

Abstract

Uncontrolled cell proliferation and genomic instability are common features of cancer and can arise from, respectively, the loss of cell-cycle control and defective checkpoints. Ubiquitin-mediated proteolysis, ultimately executed by ubiquitin-ligating enzymes (E3s), plays a key part in cell-cycle regulation and is dominated by two multisubunit E3s, the anaphase-promoting complex (or cyclosome) (APC/C) and SKP1–cullin-1–F-box (SCF) complex. We highlight the role of APC/C and the SCF bound to F-box proteins, FBXW7, SKP2, and β-TrCP, in regulating the abundance of select fundamental proteins, primarily during the cell cycle, that are associated with human cancer. The clinical success of the first proteasome inhibitor, bortezomib, in treating multiple myeloma and mantle-cell lymphoma set the precedent for viewing the ubiquitin–proteasome system as a druggable target for cancer. Given that there are more E3s than kinases, selective, small-molecule E3 inhibitors have the potential of opening up another dimension in the therapeutic armamentarium for the treatment of cancer.

Journal

Annual Review of Cancer BiologyAnnual Reviews

Published: Mar 6, 2017

There are no references for this article.