Neddylation Pathway as a Novel Anti-cancer Target: Mechanistic Investigation and Therapeutic Implication

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Neddylation Pathway as a Novel Anti-cancer Target: Mechanistic Investigation and Therapeutic Implication



Anti-Cancer Agents in Medicinal Chemistry, 15(9): 1127-1133.

Author(s): Yanan Jiang and Lijun Jia.

Affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, China.

Abstract

Protein neddylation, a newly characterized posttranslational modification that adds the ubiquitin-like molecule NEDD8 to substrates, modulates important biological processes, whereas dysfunction of neddylation may cause several serious diseases, such as cancer. Inhibition of neddylation pathway has emerged as a promising anticancer strategy, as evidenced by development of the NEDD8-activating enzyme (NAE) inhibitor MLN4924. Due to its potent anti-cancer efficacy and well-tolerated toxicity, MLN4924 has been evaluated in multiple Phase I clinical trials for solid tumors and hematologic malignancies. Recently, accumulating evidences indicate that neddylation pathway also plays a pivotal role in the regulation of multiple processes of tumor microenvironment (TME), such as tumor angiogenesis and the function of immune cells. In this review, we briefly summarize the latest progresses in this field and highlight neddylation pathway as an attractive therapeutic target against human cancer.




Keywords:

Angiogenesis, apoptosis, autophagy, neddylation, Cullin-Ring ligase, MLN4924, NEDD8-activating enzyme, senesence.



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Article Details

Volume: 15
Issue Number: 9
First Page: 1127
Last Page: 1133
Page Count: 7
DOI: 10.2174/1871520615666150305111257
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