Tid1, a cochaperone of the heat shock 70 protein and the mammalian counterpart of the Drosophila tumor suppressor 1(2)tid, is critical for early embryonic development and cell survival
Tid1, a cochaperone of the heat shock 70 protein and the mammalian counterpart of the Drosophila tumor suppressor 1(2)tid, is critical for early embryonic development and cell survival
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DOI：
10.1128/mcb.24.6.2226-2236.2004
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发表时间：
2004-03-01
影响因子：
5.3
通讯作者：
Lee, JD
中科院分区：
文献类型：
--
作者：
Lo, JF;Hayashi, M;Lee, JD
Tid 1是果蝇肿瘤抑制因子Tid 56的哺乳动物对应物，也是一种含有保守J结构域的DnaJ蛋白，它通过该结构域与伴侣蛋白的热休克蛋白70（Hsp 70）家族相互作用。我们在小鼠中产生了Tid 1条件突变，随后通过将这些条件敲除小鼠与一般删除小鼠杂交来实现Tid 1蛋白的整体去除。早在胚胎第7.5天（E7.5），未检测到Tid 1（-/-）胚胎。尽管如此，Tid 1缺陷的囊胚是可行的，孵化，形成内细胞团和滋养外胚层，并植入（E4.5），这表明纯合突变胚胎死亡之间E4.5和E7.5。为了评估Tid 1在胚胎细胞中的功能，产生了具有同源Tid 1 floxed等位基因的小鼠胚胎成纤维细胞。这些细胞中Tid 1的去除导致大量细胞死亡。Tid 1缺陷细胞的死亡可以通过野生型Tid 1的异位表达来挽救，但不能通过具有突变的J结构域的Tid 1蛋白的表达来挽救，所述Tid 1蛋白因此不能与Hsp 70结合。我们建议，Tid 1是至关重要的早期哺乳动物的发展，最有可能的功能，在维持胚胎细胞的生存，这需要它与热休克蛋白70。
Tid1 is the mammalian counterpart of the Drosophila tumor suppressor Tid56 and is also a DnaJ protein containing a conserved J domain through which it interacts with the heat shock protein 70 (Hsp70) family of chaperone proteins. We generated a Tid1 conditional mutation in mice, and the subsequent global removal of the Tid1 protein was achieved by crossing these conditional knockout mice with general deletor mice. No Tid1(-/-) embryos were detected as early as embryonic day 7.5 (E7.5). Nonetheless, Tid1-deficient blastocysts were viable, hatched, formed an inner cell mass and trophectoderm, and implanted (E4.5), suggesting that the homozygous mutant embryos die between E4.5 and E7.5. To assess the function of Tid1 in embryonic cells, mouse embryonic fibroblasts with the homologous Tid1 floxed allele were produced. Tid1 removal in these cells led to massive cell death. The death of Tid1-deficient cells could be rescued by ectopic expression of wild-type Tid1 but not by expression of the Tid1 protein that had a mutated J domain and was thus incapable of binding to Hsp70. We propose that Tid1 is critical for early mammalian development, most likely for its function in sustaining embryonic-cell survival, which requires its association with Hsp70.