Abstract
Tumor cells frequently promote the dysregulation of the cell cycle and escape from apoptotic cell death triggered by a number of cellular stresses. Programmed proteolytic degradation of regulatory proteins via the ubiquitin-proteasome pathway is crucial for homeostasis of numerous biological processes. Disruption of this system is one of the factors that promote aberrant cell-proliferation. The small ubiquitin-like protein, NEDD8, has been identified as a fundamental regulator of the activity of the E3 ubiquitin ligases called the SCF complex (consisting of Skp-1, cullin, and F-box protein) or CRL (cullin-RING ubiquitin ligase) which control a final step in ubiquitination of diverse substrates associated with cancer biology. The ubiquitin ligase activity of the SCF complex requires NEDD8 to covalently bind to cullins. To a large extent, exploring the negative regulation system of the NEDD8 pathway is expected to lead to the development of novel anticancer targets. This review focuses on the NEDD8 negative regulation system including chemical compounds such as MLN4924 and protein molecules (e.g. COP9 signalosome, CAND1, inactive mutant of Ubc12 and NUB1/NUB1L) and clarifies possible strategies for targeting the NEDD8 cascade in cancer cells.
Keywords: Ubiquitination, SCF complex, NEDD8, MLN4924, COP9 signalosome, CAND1, NUB1/NUB1L.
Current Pharmaceutical Design
Title:Negative Regulation of NEDD8 Conjugation Pathway by Novel Molecules and Agents for Anticancer Therapy
Volume: 19 Issue: 22
Author(s): Tomoaki Tanaka, Tatsuya Nakatani and Tetsu Kamitani
Affiliation:
Keywords: Ubiquitination, SCF complex, NEDD8, MLN4924, COP9 signalosome, CAND1, NUB1/NUB1L.
Abstract: Tumor cells frequently promote the dysregulation of the cell cycle and escape from apoptotic cell death triggered by a number of cellular stresses. Programmed proteolytic degradation of regulatory proteins via the ubiquitin-proteasome pathway is crucial for homeostasis of numerous biological processes. Disruption of this system is one of the factors that promote aberrant cell-proliferation. The small ubiquitin-like protein, NEDD8, has been identified as a fundamental regulator of the activity of the E3 ubiquitin ligases called the SCF complex (consisting of Skp-1, cullin, and F-box protein) or CRL (cullin-RING ubiquitin ligase) which control a final step in ubiquitination of diverse substrates associated with cancer biology. The ubiquitin ligase activity of the SCF complex requires NEDD8 to covalently bind to cullins. To a large extent, exploring the negative regulation system of the NEDD8 pathway is expected to lead to the development of novel anticancer targets. This review focuses on the NEDD8 negative regulation system including chemical compounds such as MLN4924 and protein molecules (e.g. COP9 signalosome, CAND1, inactive mutant of Ubc12 and NUB1/NUB1L) and clarifies possible strategies for targeting the NEDD8 cascade in cancer cells.
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Cite this article as:
Tanaka Tomoaki, Nakatani Tatsuya and Kamitani Tetsu, Negative Regulation of NEDD8 Conjugation Pathway by Novel Molecules and Agents for Anticancer Therapy, Current Pharmaceutical Design 2013; 19 (22) . https://dx.doi.org/10.2174/1381612811319220017
DOI https://dx.doi.org/10.2174/1381612811319220017 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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