COTRANSLATION OF ACTIVATED MUTANT P53 WITH WILD-TYPE DRIVES THE WILD-TYPE P53 PROTEIN INTO THE MUTANT CONFORMATION
COTRANSLATION OF ACTIVATED MUTANT P53 WITH WILD-TYPE DRIVES THE WILD-TYPE P53 PROTEIN INTO THE MUTANT CONFORMATION
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DOI：
10.1016/0092-8674(91)90384-b
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发表时间：
1991-05-31
期刊：
影响因子：
64.5
通讯作者：
MEDCALF, EA
中科院分区：
文献类型：
--
作者：
MILNER, J;MEDCALF, EA
p53的激活突变促进肿瘤进展。 突变蛋白采用特征构象，其缺乏野生型p53的生长抑制功能。 我们发现突变型p53可以驱动共翻译的野生型p53突变体构象：在体内类似的效果将阻断野生型抑制功能与显性负效应。 突变型p53对野生型构象的共翻译作用依赖于新生多肽之间的相互作用和全长蛋白质的寡聚化。 我们还表明，p53蛋白的寡聚体可以被诱导以合作的方式改变构象。 细胞生长刺激诱导p53类似的构象变化，我们目前的研究结果表明，这可能涉及变构调节。
Activating mutations of p53 promote tumor progression. The mutant protein adopts a characteristic conformation, which lacks the growth suppressor function of wild-type p53. We show that mutant p53 can drive cotranslated wild-type p53 into the mutant conformation: a similar effect in vivo would block wild-type suppressor function with dominant negative effect. The cotranslational effect of mutant p53 on wild-type conformation depends upon interaction between nascent polypeptides and oligomerization of the full-length proteins. We also show that oligomers of p53 proteins can be induced to change conformation in a cooperative manner. Cell growth stimulation induces a similar conformational change in p53, and our present results indicate that this may involve allosteric regulation.