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首页> 外文期刊>Molecular and Cellular Biology >Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53.
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Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53.

机译：人DNA激活的蛋白激酶在人p53的氨基末端反式激活域中将丝氨酸15和37磷酸化。

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摘要

Human DNA-PK is a nuclear, serine/threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding substrates, including the tumor suppressor protein p53. To identify which p53 residues are phosphorylated, we examined DNA-PK's ability to phosphorylate synthetic peptides corresponding to human p53 sequences. Serines 15 and 37 in the amino-terminal transactivation domain of human p53, and serines 7 and 18 of mouse p53, were phosphorylated by DNA-PK in the context of synthetic peptides. Other serines in these p53 peptides, and serines in other p53 peptides, including peptides containing the serine 315 p34cdc2 site and the serine 392 casein kinase II site, were not recognized by DNA-PK or were phosphorylated less efficiently. Phosphorylation of the conserved serine 15 in human p53 peptides depended on the presence of an adjacent glutamine, and phosphorylation was inhibited by the presence of a nearby lysine. Phosphorylation of recombinant wild-type mouse p53 was inhibited at high DNA concentrations, suggesting that DNA-PK may phosphorylate p53 only when both are bound to DNA at nearby sites. Our study suggests that DNA-PK may have a role in regulating cell growth and indicates how phosphorylation of serine 15 in DNA-bound p53 could alter p53 function.
机译：人DNA-PK是一种核的丝氨酸/苏氨酸蛋白激酶，当被DNA激活时会磷酸化几种DNA结合底物，包括肿瘤抑制蛋白p53。为了确定哪些p53残基被磷酸化，我们检查了DNA-PK磷酸化对应于人p53序列的合成肽的能力。在合成肽的背景下，人p53氨基末端反式激活域中的丝氨酸15和37，以及小鼠p53的丝氨酸7和18被DNA-PK磷酸化。这些p53肽中的其他丝氨酸，以及其他p53肽中的丝氨酸，包括含有丝氨酸315 p34cdc2位点和丝氨酸392酪蛋白激酶II位点的肽，都无法被DNA-PK识别或磷酸化效率较低。人p53肽中保守丝氨酸15的磷酸化取决于相邻谷氨酰胺的存在，而附近赖氨酸的存在则抑制了磷酸化。重组野生型小鼠p53的磷酸化在高DNA浓度下受到抑制，这表明DNA-PK仅在两者都与附近位置的DNA结合时才可能使p53磷酸化。我们的研究表明，DNA-PK可能在调节细胞生长中起作用，并表明与DNA结合的p53中丝氨酸15的磷酸化如何改变p53的功能。

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