Flaman J M, Waridel F, Estreicher A, Vannier A, Limacher J M, Gilbert D, Iggo R, Frebourg T
Laboratoire de Génétique Moléculaire, CHU de Rouen, France.
Oncogene. 1996 Feb 15;12(4):813-8.
Alternative splicing affecting the p53 carboxy-terminus has previously been described in mouse but not in normal human cells. We report here the detection in normal human lymphocytes of an alternatively spliced form of human p53 mRNA containing an additional 133 bp exon derived from intron 9. This splice variant encodes a truncated protein of 341 amino-acids including 10 new amino-acids derived from the novel exon. The truncated protein, which lacks part of the p53 tetramerization domain, fails to bind DNA in vitro and has a transcriptional defect in vivo in both yeast and mammalian cells. Quantitative RT-PCR experiments suggest that the alternatively spliced form is only present in significant amounts in quiescent cells. Considering the numerous functions ascribed to the carboxy-terminus of the p53 protein, this splice variant may have important implications for the biological role of p53 in normal cells.
此前在小鼠中已发现影响p53羧基末端的可变剪接，但在正常人类细胞中尚未发现。我们在此报告，在正常人类淋巴细胞中检测到一种人类p53 mRNA的可变剪接形式，该形式包含一个额外的133 bp外显子，其来源于内含子9。这种剪接变体编码一种341个氨基酸的截短蛋白，其中包括10个源自新外显子的新氨基酸。该截短蛋白缺少部分p53四聚化结构域，在体外无法结合DNA，并且在酵母和哺乳动物细胞的体内均存在转录缺陷。定量RT-PCR实验表明，这种可变剪接形式仅在静止细胞中大量存在。鉴于p53蛋白羧基末端具有多种功能，这种剪接变体可能对p53在正常细胞中的生物学作用具有重要影响。
