Targeting MDM4 Splicing in Cancers

被引：21

作者：

Bardot, Boris ^{[1
]}

Toledo, Franck ^{[1
]}

机构：

[1] PSL Res Univ, Sorbonne Univ, UPMC Univ Paris 06,Inst Curie,Ctr Rech, CNRS UMR 3244,Genet Suppress Tumorale,Equipe Lab, 26 Rue Ulm, F-75248 Paris 05, France

来源：

GENES | 2017年 / 8卷 / 02期

关键词：

MDM4; MDM2; p53; alternative splicing; isoform; PRE-MESSENGER-RNA; THERAPEUTIC TARGET; P53; INHIBITION; BCL-X; DOMAIN; MICE; EXPRESSION; REVEALS; CELLS; GENE;

D O I：

10.3390/genes8020082

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

MDM4, an essential negative regulator of the P53 tumor suppressor, is frequently overexpressed in cancer cells that harbor a wild-type P53. By a mechanism based on alternative splicing, the MDM4 gene generates two mutually exclusive isoforms: MDM4-FL, which encodes the full-length MDM4 protein, and a shorter splice variant called MDM4-S. Previous results suggested that the MDM4-S isoform could be an important driver of tumor development. In this short review, we discuss a recent set of data indicating that MDM4-S is more likely a passenger isoform during tumorigenesis and that targeting MDM4 splicing to prevent MDM4-FL protein expression appears as a promising strategy to reactivate p53 in cancer cells. The benefits and risks associated with this strategy are also discussed.

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页数：6

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