Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma
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- 作者：Mouadh Benamara ; Fadila Guessousa ; Kangping Dua ; Patrick Corbetta ; Joseph Obeidb ; Daniel Gioelic ; Craig L. Slingluff Jrb ; Tarek Abbasa ; d ; e ; ta8e@virginia.edu" class="auth_mail" title="E-mail the corresponding author
- 关键词：Melanoma ; CDT2 ; DTL ; Cullin ; Ubiquitylation ; MLN4924 ; Pevonedistat ; BRAF ; NRAS
- 刊名：EBioMedicine
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：10
- 期：Complete
- 页码：85-100
- 全文大小：3172 K
文摘
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CDT2 is overexpressed in melanoma, and correlates with poor patient survival.
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CDT2 ablation in melanoma induces p21- and Set8-dependent rereplication.
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Pevonedistat suppresses melanoma in vitro and in vivo through stabilizing SET8 and p21.
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Pevonedistat synergizes with PLX4720 to suppress BRAF melanoma and inhibits PLX4720-resistant cells.