State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
Biochem Biophys Res Commun. 2011 Apr 1;407(1):86-91. doi: 10.1016/j.bbrc.2011.02.114. Epub 2011 Feb 28.
PIDD1 (P53-induced death domain) is a pro-apoptotic gene which can be induced by p53. So far, three alternative splicing products of human PIDD gene have been identified. Here we report a new splicing variant of this gene and named it PIDD4. The coding sequence of PIDD4 contains intron 3 and a 60 bp insert at the 5' of exon 3. Each insertion has an in-frame stop codon, which makes PIDD4 get translated from exon 5 then. Therefore, PIDD4 protein lacks the 32 KD N-terminal peptide, missing the LRR domain found in the other three isoforms. In this study, we have shown that the expression of PIDD4 is also regulated by p53, and as PIDD2, it is not expressed in heart either. Moreover, PIDD4 is the only isoform which is expressed in skeletal muscle. This isoform mainly localizes in the cytoplasm, and produces a relatively higher proportion of PIDD-CC fragment. Overexpression of PIDD4 independently promotes apoptosis.
PIDD1（P53 诱导死亡结构域）是一种促凋亡基因，可被 p53 诱导。迄今为止，已鉴定出人 PIDD 基因的三种选择性剪接产物。在这里，我们报告了该基因的一个新的剪接变体，并将其命名为 PIDD4。PIDD4 的编码序列包含内含子 3 和外显子 3 5'端的 60bp 插入。每个插入都有一个框内终止密码子，这使得 PIDD4 从外显子 5 开始翻译。因此，PIDD4 蛋白缺失了 32KD 的 N 端肽，缺失了其他三种异构体中发现的 LRR 结构域。在这项研究中，我们已经表明 PIDD4 的表达也受 p53 调控，并且与 PIDD2 一样，它在心脏中也不表达。此外，PIDD4 是唯一在骨骼肌中表达的异构体。这种异构体主要定位于细胞质中，并产生相对较高比例的 PIDD-CC 片段。PIDD4 的过表达可独立促进细胞凋亡。
