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p53 肿瘤抑制样蛋白 nvp63 介导海葵 Nematostella vectensis 中选择性的生殖细胞死亡。

The p53 tumor suppressor-like protein nvp63 mediates selective germ cell death in the sea anemone Nematostella vectensis.

机构信息

Department of Cell Biology, The Scripps Research Institute, La Jolla, California, United States of America.

出版信息

PLoS One. 2007 Sep 12;2(9):e782. doi: 10.1371/journal.pone.0000782.

Abstract

Here we report the identification and molecular function of the p53 tumor suppressor-like protein nvp63 in a non-bilaterian animal, the starlet sea anemone Nematostella vectensis. So far, p53-like proteins had been found in bilaterians only. The evolutionary origin of p53-like proteins is highly disputed and primordial p53-like proteins are variably thought to protect somatic cells from genotoxic stress. Here we show that ultraviolet (UV) irradiation at low levels selectively induces programmed cell death in early gametes but not somatic cells of adult N. vectensis polyps. We demonstrate with RNA interference that nvp63 mediates this cell death in vivo. Nvp63 is the most archaic member of three p53-like proteins found in N. vectensis and in congruence with all known p53-like proteins, nvp63 binds to the vertebrate p53 DNA recognition sequence and activates target gene transcription in vitro. A transactivation inhibitory domain at its C-terminus with high homology to the vertebrate p63 may regulate nvp63 on a molecular level. The genotoxic stress induced and nvp63 mediated apoptosis in N. vectensis gametes reveals an evolutionary ancient germ cell protective pathway which relies on p63-like proteins and is conserved from cnidarians to vertebrates.

摘要

在这里,我们在一种非两侧对称动物——星状海葵(Nematostella vectensis)中鉴定并研究了 p53 肿瘤抑制样蛋白 nvp63 的分子功能。迄今为止,p53 样蛋白仅在两侧对称动物中被发现。p53 样蛋白的进化起源存在很大争议,人们普遍认为原始的 p53 样蛋白可以保护体细胞免受遗传毒性应激。在这里,我们发现低剂量的紫外线(UV)辐射选择性地诱导早期配子中的程序性细胞死亡,但不会诱导成年 N. vectensis 水螅体的体细胞死亡。我们通过 RNA 干扰证明 nvp63 在体内介导了这种细胞死亡。nvp63 是在 N. vectensis 中发现的三种 p53 样蛋白中最古老的成员,与所有已知的 p53 样蛋白一致,nvp63 与脊椎动物 p53 DNA 识别序列结合,并在体外激活靶基因转录。其 C 端具有与脊椎动物 p63 高度同源的转录抑制结构域,可能在分子水平上调节 nvp63。N. vectensis 配子中的遗传毒性应激诱导和 nvp63 介导的细胞凋亡揭示了一种古老的生殖细胞保护途径,该途径依赖于 p63 样蛋白,从刺胞动物到脊椎动物都是保守的。

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