p53 is a regulator of macrophage differentiation
p53 is a regulator of macrophage differentiation
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DOI：
10.1038/sj.cdd.4401379
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发表时间：
2004-04-01
影响因子：
12.4
通讯作者：
Rotter, V
中科院分区：
文献类型：
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作者：
Matas, D;Milyavsky, M;Rotter, V
虽然p53在细胞凋亡中起作用已被广泛接受，但其参与细胞分化的情况知之甚少。在这里，我们表明，野生型p53促进IL-6依赖的巨噬细胞分化。以野生型构象处理表达温度敏感性p53 143（瓦尔至Ala）突变体的M1/2细胞，促进了表现出吞噬活性的成熟巨噬细胞的出现。野生型构象的p53 143（瓦尔至Ala）的分化增强与该蛋白对凋亡诱导的抑制相结合。与以前的研究一致，我们发现p53依赖性巨噬细胞分化过程中p53水平降低。这发生在IL-6刺激前p53水平高时。有趣的是，p53 143（瓦尔到Ala）蛋白，在突变体构象，增强巨噬细胞分化，野生型构象，而p53 273（Arg到His）核心突变体对这一途径产生抑制作用。转录缺陷型p53分子p53（22 - 23）和p53 22，23，143不能诱导p53依赖性分化。此外，p53（22 - 23）蛋白抑制p53非依赖性分化途径。有趣的是，p53（22 - 23）蛋白不仅阻断IL-6介导的分化，而且在IL-6刺激后诱导显著的凋亡性细胞死亡。两者合计，我们的数据表明，野生型p53增强巨噬细胞分化，而各种p53突变型发挥不同的影响，这一分化途径。
While it is well accepted that p53 plays a role in apoptosis, less is known as to its involvement in cell differentiation. Here we show that wild-type p53 facilitates IL-6-dependent macrophage differentiation. Treatment of M1/2 cells expressing the temperature-sensitive p53 143 (Val to Ala) mutant, at the wild-type conformation, facilitated the appearance of mature macrophages that exhibited phagocytic activity. Enhancement of differentiation by the p53 143 ( Val to Ala) in the wild-type conformation was coupled with the inhibition of apoptosis induction by this protein. In agreement with previous studies, we found that p53 levels were reduced during p53-dependent macrophage differentiation. This occurred when p53 levels before IL-6 stimuli were high. Interestingly, the p53 143 ( Val to Ala) protein, at the mutant conformation, enhanced macrophage differentiation, as did the wild-type conformation, whereas the p53 273 (Arg to His) core mutant exerted an inhibitory effect on this pathway. The transcription-deficient p53 molecules, p53 ( 22 - 23) and p53 22,23,143, could not induce p53-dependent differentiation. Moreover, the p53 ( 22 - 23) protein inhibited the p53-independent differentiation pathway. Interestingly, the p53 ( 22 - 23) protein not only blocked IL-6-mediated differentiation, but also induced significant apoptotic cell death, upon IL-6 stimulation. Taken together, our data show that wild-type p53 enhances macrophage differentiation, while various p53 mutant types exert different effects on this differentiation pathway.