Mutation of the casein kinase II phosphorylation site abolishes the anti-proliferative activity of p53.
Mutation of the casein kinase II phosphorylation site abolishes the anti-proliferative activity of p53.
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DOI：
10.1093/nar/20.21.5565
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发表时间：
1992-11
影响因子：
14.9
通讯作者：
D. Milne;Ruth H. Palmer;David W. Meek
中科院分区：
文献类型：
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作者：
D. Milne;Ruth H. Palmer;David W. Meek
P53肿瘤抑制蛋白被几种蛋白激酶磷酸化，包括酪蛋白激酶II。为了了解酪蛋白激酶II磷酸化的功能意义，我们在小鼠P53中引入了丝氨酸386位突变，并研究了它们对P53抑制细胞生长能力的影响。丝氨酸386被丙氨酸取代导致生长抑制活性的丧失，而该位置的天冬氨酸部分保留了抑制功能。这些数据表明，P53的抗增殖活性是由丝氨酸386位的磷酸化激活的，并在哺乳动物细胞中建立了生长抑制蛋白的共价修饰与其活性调节之间的直接联系。
The p53 tumour suppressor protein is phosphorylated by several protein kinases, including casein kinase II. In order to understand the functional significance of phosphorylation by casein kinase II, we have introduced mutations at serine 386 in mouse p53, the residue phosphorylated by this kinase, and investigated their effects on the ability of p53 to arrest cell growth. Replacement of serine 386 by alanine led to loss of growth suppressor activity, while aspartic acid at this position partially retained suppressor function. These data suggest that the anti-proliferative activity of p53 is activated by phosphorylation at serine 386, and establish a direct link between the covalent modification of a growth suppressor protein and regulation of its activity in mammalian cells.