Central role of p53 in the suntan response and pathologic hyperpigmentation
Central role of p53 in the suntan response and pathologic hyperpigmentation
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DOI：
10.1016/j.cell.2006.12.045
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发表时间：
2007-03-09
期刊：
影响因子：
64.5
通讯作者：
Fisher, David E.
中科院分区：
文献类型：
--
作者：
Cui, Rutao;Widlund, Hans R.;Fisher, David E.
紫外线诱导的色素沉着（晒黑）需要角化细胞诱导α -促黑素细胞激素（α - msh）的分泌，α - msh和其他生物活性肽是促黑素皮质素（POMC）的裂解产物。在这里，我们提供了生化和遗传学证据，证明紫外线诱导皮肤中POMC/MSH是由p53直接控制的。尽管p53在紫外线作用下能有效刺激POMC启动子，但在基因敲除小鼠中，p53的缺失与紫外线晒黑反应的缺失有关。同样的途径产生-内啡肽，另一种POMC衍生物，可能有助于寻求阳光的行为。此外，几个不依赖紫外线的病理性色素沉着的例子显示涉及p53“模仿”晒黑反应。因此，P53作为紫外线色素沉着的传感器/效应器，这是一个几乎恒定的环境暴露。此外，这一途径在病理性色素沉着的许多条件下被激活，从而模仿晒黑反应。
UV-induced Pigmentation (suntanning) requires induction of a-melanocyte-stimulating hormone (alpha-MSH) secretion by keratinocytes- alpha-MSH and other bioactive pepticles are cleavage products Of pro-opiomelanocortin (POMC). Here we Provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces beta-endorphin, another POMC derivative, which potentially contributes to sun-seeking behaviors. Furthermore, several instances of UV-independent pathologic Pigmentation are shown to involve p53 "mimicking" the tanning response. P53 thus functions as a sensor/effector for UV Pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response.