The α/β carboxy-terminal domains of p63 are required for skin and limb development. New insights from the Brdm2 mouse which is not a complete p63 knockout but expresses p63 γ-like proteins
The α/β carboxy-terminal domains of p63 are required for skin and limb development. New insights from the Brdm2 mouse which is not a complete p63 knockout but expresses p63 γ-like proteins
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DOI：
10.1038/cdd.2009.25
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发表时间：
2009-08-01
影响因子：
12.4
通讯作者：
Moll, U. M.
中科院分区：
文献类型：
--
作者：
Wolff, S.;Talos, F.;Moll, U. M.
p63是p53家族的祖先转录因子，具有三种C-末端同种型，其相对的体内功能是难以捉摸的。p63基因对皮肤和肢体发育至关重要，两个独立的整体敲除小鼠模型生动地显示了这一点。这两种菌株，虽然构建不同，有相同的和严重的表型，其特点是缺乏表皮和后肢和只有不发达的前肢在出生时。在这里，我们表明，小鼠从一个模型，Brdm 2，表达正常水平的截短的p63蛋白，含有DNA结合和寡聚化结构域，但缺乏长的羧基末端SAM（无菌α基序）和后SAM结构域，是特定的α和β亚型。因此，来自Brdm 2小鼠的转录活性p63蛋白类似于天然存在的p63 γ同种型，其在所有p63同种型中最接近于p53。因此，Brdm 2小鼠是p63 α/β亚型特异性敲除小鼠，获得了意想不到的新重要性。我们的研究表明，p63 α/β而不是p63 γ是皮肤和肢体发育所必需的。Cell Death and Differentiation（2009）16，1108-1117; doi：10.1038/cdd.2009.25; 2009年3月20日在线发表
p63, an ancestral transcription factor of the p53 family, has three C-terminal isoforms whose relative in vivo functions are elusive. The p63 gene is essential for skin and limb development, as vividly shown by two independent global knockout mouse models. Both strains, although constructed differently, have identical and severe phenotypes, characterized by absent epidermis and hindlimbs and only rudimentary forelimbs at birth. Here we show that mice from one model, Brdm2, express normal levels of truncated p63 proteins that contain the DNA binding and oligomerization domain but lack the long carboxy-terminal SAM (sterile alpha-motif) and post-SAM domains that are specific for the alpha and beta isoforms. As such, transcriptionally active p63 proteins from Brdm2 mice resemble the naturally occurring p63 gamma isoforms, which of all the p63 isoforms most closely resemble p53. Thus, Brdm2 mice are p63 alpha/beta isoform-specific knockout mice, gaining unexpected new importance. Our studies identify that p63 alpha/beta but not p63 gamma are absolutely required for proper skin and limb development. Cell Death and Differentiation (2009) 16, 1108-1117; doi:10.1038/cdd.2009.25; published online 20 March 2009