Cisplatin binds to the MDM2 RING finger domain and inhibits the ubiquitination activity.

Kaiming Cao, Xin Ding, Yaping Sheng, Yu Wang, Yangzhong Liu

Chemical communications (Cambridge, England) 2020 Apr 28

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Cisplatin can directly bind to the RING finger domain of MDM2, leading to the zinc-release and protein unfolding. Consequently, cisplatin inhibits the MDM2-mediated ubiquitination, which is the molecular basis of p53 activation. This work provides insight into the cisplatin-induced p53-elevation that is involved in cell apoptosis.

Citation

Kaiming Cao, Xin Ding, Yaping Sheng, Yu Wang, Yangzhong Liu. Cisplatin binds to the MDM2 RING finger domain and inhibits the ubiquitination activity. Chemical communications (Cambridge, England). 2020 Apr 28;56(33):4599-4602