Stabilization of the MDM2 oncoprotein by mutant p53
Stabilization of the MDM2 oncoprotein by mutant p53
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DOI：
10.1074/jbc.c000781200
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发表时间：
2001-03-02
影响因子：
4.8
通讯作者：
Chen, JD
中科院分区：
文献类型：
--
作者：
Peng, YH;Chen, LH;Chen, JD
MDM2是一种调节P53降解的短命蛋白。我们在此报道了MDM2和几个P53热点突变体的瞬时共表达导致MDM2的稳定和表达增加。通过重组腺病毒感染或稳定表达突变型p53(175H)等位基因也可以稳定p53阴性细胞中的内源性MDM2。与p53缺失细胞相比，一组表达不同内源性突变型p53等位基因的人类肿瘤细胞系也含有稳定的核MDM2。在肿瘤细胞中，MDM2存在于与突变型p53的复合体中，稳定MDM2需要与突变型p53直接结合。这些结果揭示了突变型P53的一种新特性和带有P53错义突变的肿瘤的独特特征。稳定的MDM2的积聚可能通过其不依赖于P53的转化功能参与肿瘤的发生。
MDM2 is a short-lived protein that regulates p53 degradation. We report here that transient coexpression of MDM2 and several p53 hotspot mutants resulted in stabilization and increased expression of MDM2. Ectopic expression of the mutant p53(175H) allele by recombinant adenovirus infection or stable transfection also stabilized endogenous MDM2 in p53-null cells. A panel of human tumor cell lines expressing different endogenous mutant p53 alleles also contained stabilized nuclear MDM2 at elevated levels when compared with p53 null cells. MDM2 was present in complexes with mutant p53 in tumor cells, and stabilization of MDM2 required direct binding to mutant p53. These results reveal a novel property of mutant p53 and a unique feature of tumors with p53 missense mutations. Accumulation of stable MDM2 may contribute to tumorigenesis through its p53-independent transforming functions.