Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53.
Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53.
复制标题
致瘤突变体 p53 对应激诱导激酶途径的抑制。
DOI：
10.1128/mcb.23.1.322-334.2003
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发表时间：
2003
影响因子：
5.3
通讯作者：
Horikoshi,Nobuo
中科院分区：
文献类型：
--
作者：
Ohiro,Yoichi;Usheva,Anny;Kobayashi,Shinichiro;Duffy,ShannonL;Nantz,Regan;Gius,David;Horikoshi,Nobuo
More than 50% of human cancers contain p53 gene mutations and as a result accumulate altered forms of the full-length p53 protein. Although certain tumor types expressing mutant p53 protein have a poor prognostic process, the precise role of mutant p53 protein in highly malignant tumor cells is not well defined. Some p53 mutants, but not wild-type p53, are shown here to interact with Daxx, a Fas-binding protein that activates stress-inducible kinase pathways. Interaction of Daxx with p53 is highly dependent upon the specific mutation of p53. Tumorigenic mutants of p53 bind to Daxx and inhibit Daxx-dependent activation of the apoptosis signal-regulating kinase 1 stress-inducible kinases and Jun NH2-terminal kinase. Mutant p53 forms complexes with Daxx in cells, and consequently, mutant p53 is able to rescue cells from Daxx-dependent inhibition of proliferation. Thus, the accumulation of mutant p53 in tumor cells may contribute to tumorigenesis by inhibiting stress-inducible kinase pathways.
