The point mutation that substitutes lysine with arginine at position 120 of human p53 has been characterized as a missense mutation. The K120R mutation renders the p53 protein disabled for acetylation and, as a result, defective for apoptotic function, which provides a mechanistic link between the missense mutation and tumorigenesis. However, we noticed the failures of tumorigenesis in mice with the mutation, and of the related studies to notice that it has arbitrarily reflected in amino acid change through a sequence modification (AGA) of the original tumor mutation (AGG) by codon degeneracy. Unlike this modified version, we also discovered a novel splicing site the original mutation, TP53 c.359A>G, may induce. Using a human induced pluripotent stem cell line that was engineered to be homozygous for the original mutation, we here identified that the accidental splicing site generates a defective transcript variant with a frame-shifted premature termination codon which is subjected to nonsense-mediated mRNA decay. The authentic splicing still occurs but in extremely low amounts. Taken together, this mutation causes depletion of cellular p53 via defective mRNA, suggesting a new link to tumorigenesis.

中文翻译：

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K120R突变通过产生异常的剪接位点使p53失活，从而导致无意义的mRNA降解。

在人p53的120位上用精氨酸替代赖氨酸的点突变已被表征为错义突变。K120R突变使p53蛋白无法乙酰化，结果导致凋亡功能缺陷，这在错义突变和肿瘤发生之间提供了机械联系。但是，我们注意到具有该突变的小鼠的肿瘤发生失败，并且相关研究注意到它已通过密码子简并性通过原始肿瘤突变（AGG）的序列修饰（AGA）任意反映在氨基酸变化中。与该修饰版本不同，我们还发现了一个新的剪接位点，其原始突变TP53 c.359A> G可以诱导。使用人类诱导的多能干细胞系，该细胞系针对原始突变被设计为纯合的，我们在这里发现偶然的剪接位点产生了一个缺陷的转录变异体，该变异体具有移码的过早终止密码子，该密码子会发生无意义的mRNA衰变。真实的拼接仍然发生，但是数量很少。综上所述，这种突变通过有缺陷的mRNA引起细胞p53的耗竭，这暗示了与肿瘤发生的新联系。