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非洲爪蟾两个bcl-2样细胞存活基因的克隆、特性分析及表达

Cloning, characterization and expression of two Xenopus bcl-2-like cell-survival genes.

作者信息

Cruz-Reyes J, Tata J R

机构信息

Division of Developmental Biochemistry, National Institute for Medical Research, Mill Hill, London, UK.

出版信息

Gene. 1995 Jun 9;158(2):171-9. doi: 10.1016/0378-1119(95)00159-4.

DOI:10.1016/0378-1119(95)00159-4
PMID:7607538
Abstract

We describe two cloned cDNAs, termed xR1 and xR11, isolated from a Xenopus laevis stage 28-30 embryonic head cDNA library. Comparison of amino acid (aa) sequences derived from nucleotide (nt) sequences of xR1 and xR11 cDNAs revealed substantial homology with bcl-2-related genes, especially with bcl-xL. In particular, there was a marked conservation of the BH1 and BH2 domains considered to be important for the anti-cell death and heterodimerisation properties of bcl-2. Constitutive expression of xR11 in cultured rat fibroblast (Rat-1) cells conferred a strong protection against cell death induced by the cytotoxic agents staurosporine and cycloheximide, by serum deprivation and specific deregulation of c-myc. Measurement of xR1 and xR11 mRNAs by RNase protection assay revealed similar widespread expression in Xenopus embryos and tadpoles. Except for an abrupt increase in the accumulation of xR1 and xR11 mRNAs in brains of mid-metamorphic and post-metamorphic tadpoles and adults, there was insignificant modulation of their expression in tissues undergoing total regression (tail) or morphogenesis (limb) during natural or thyroid hormone-induced metamorphosis. These findings raise the possibility of continuing expression of cell survival genes in tissues undergoing total regression during post-embryonic development.

摘要

我们描述了从非洲爪蟾28 - 30期胚胎头部cDNA文库中分离得到的两个克隆的cDNA,分别命名为xR1和xR11。对由xR1和xR11 cDNA的核苷酸(nt)序列推导而来的氨基酸(aa)序列进行比较,发现它们与bcl - 2相关基因具有显著同源性,尤其是与bcl - xL。特别地,被认为对bcl - 2的抗细胞死亡和异源二聚化特性很重要的BH1和BH2结构域存在明显保守性。在培养的大鼠成纤维细胞(Rat - 1)中组成型表达xR11,可对由细胞毒性剂星形孢菌素和放线菌酮、血清剥夺以及c - myc的特异性失调诱导的细胞死亡提供强大保护。通过核糖核酸酶保护分析测定xR1和xR11 mRNA,发现在非洲爪蟾胚胎和蝌蚪中它们的表达分布相似。除了在变态中期和变态后期的蝌蚪及成体的大脑中xR1和xR11 mRNA的积累突然增加外,在自然或甲状腺激素诱导的变态过程中,它们在经历完全退化(尾巴)或形态发生(肢体)的组织中的表达没有明显调节。这些发现增加了在胚胎后发育过程中经历完全退化的组织中细胞存活基因持续表达的可能性。

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