Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma

Jiyou Wang, Shiwen Wang, Wenjuan Zhang, Xiaofang Wang, Xiaojun Liu, Liang Liu, Lihui Li, Yupei Liang, Jinha Yu, Lak Shin Jeong, Lijun Jia, Hu Zhao, Yanmei Zhang

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11 Scopus citations


Inhibition of protein neddylation pathway has emerged an attractive anticancer strategy in preclinical studies by using Nedd8-activating enzyme (NAE) inhibitor MLN4924 (Pevonedistat). Previous studies have reported the antitumor activity of MLN4924 mediated by its efficacy on apoptosis, autophagy and senescence. However, whether MLN4924 has any effect on renal carcinoma cells (RCC) remains unexplored. Here we reported that MLN4924 specifically inhibited protein neddylation pathway, leading to statistically significantly suppress the proliferation, survival and migration of RCC cells by inducing G2 cell-cycle arrest, followed by apoptosis in a MLN4924 dose-dependent manner. Further mechanistic study revealed that MLN4924-induced apoptosis was mediated by substantial up-regulation of pro-apoptotic NOXA. These findings highlighted the anticancer effects of the neddylation inhibitors (e.g. MLN4924) for the treatment of RCC.

Original languageEnglish
Pages (from-to)1183-1188
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - 2 Sep 2017

Bibliographical note

Funding Information:
This work was supported by the Chinese Minister of Science and Technology grant [grant numbers 2016YFA0501800], National Natural Science Foundation Grant of China [grant numbers: 81602072, 81625081, 81372196, 81572340, 81400893], the “Shuguang Program” supported by Shanghai Education Development Foundation [grant numbers: 14SG07], the “Shanghai Sailing Program” [grant numbers: 2017YF1405000], and Shanghai Municipal Commission of Health and Family Planning, Key developing disciplines [grant numbers: 2015ZB0501].

Publisher Copyright:
© 2017


  • Apoptosis
  • MLN4924
  • Neddylation
  • Renal cell carcinoma


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