关于MDM2/MDM4异二聚体的新见解。
Novel insights about the MDM2/MDM4 heterodimer.
作者信息
Moretti Fabiola
机构信息
Institute of Cell Biology and Neurobiology, National Research Council of Italy , Roma, Italy.
出版信息
Mol Cell Oncol. 2015 Aug 20;3(2):e1066923. doi: 10.1080/23723556.2015.1066923. eCollection 2016 Mar.
Abstract
MDM2 (mouse double minute 2 homolog) and MDM4 (double minute 4 human homolog, also known as MDMX) inhibit the activity of tumor protein p53 (TP53, best known as p53) through their heterodimerization. New evidence indicates that under stress conditions the heterodimer is modified, leading to different activities of the single molecules. In particular, following lethal DNA damage, MDM2 and MDM4 dissociate and MDM4 promotes the stabilization of homeodomain-interacting protein kinase 2 (HIPK2) and the phosphorylation of p53, resulting in transcriptional repression of antiapoptotic targets of p53/HIPK2.
摘要
MDM2（小鼠双微体2同源物）和MDM4（人双微体4同源物，也称为MDMX）通过异二聚化抑制肿瘤蛋白p53（TP53，通常称为p53）的活性。新证据表明，在应激条件下，异二聚体发生修饰，导致单个分子具有不同的活性。特别是，在致死性DNA损伤后，MDM2和MDM4解离，MDM4促进同源结构域相互作用蛋白激酶2（HIPK2）的稳定以及p53的磷酸化，导致p53/HIPK2抗凋亡靶标的转录抑制。
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