Ding Vivianne W, Lin Li-Ping, Chiang Andrew L, McCormick Frank
UCSF Comprehensive Cancer Center, Cancer Research Institute, 2340 Sutter Street, San Francisco, CA 94115, USA.
J Mol Med (Berl). 2007 Nov;85(11):1281-9. doi: 10.1007/s00109-007-0228-8. Epub 2007 Jun 26.
Dishevelled is a key component of the Wnt signaling and planar polarity pathways. We discovered that in selective cell types, it potently activates the transcriptional activity of the tumor suppressor p53. This action, however, is not dependent on the downstream of either the Wnt or the planar polarity pathways. Dishevelled signals to the first 50 amino acids of p53, which is the transactivation domain. The level of phosphorylation on several serine residues within that region of p53 increases in response to disheveled activation, partially contributing to p53 activation. The MAP kinase pathway and E1B55k may also be involved in this dishevelled-p53 connection. Our data provide evidence that there is a novel signaling pathway from Dishevelled to p53.
Dishevelled是Wnt信号通路和平面极性通路的关键组成部分。我们发现，在某些特定细胞类型中，它能有效激活肿瘤抑制因子p53的转录活性。然而，这一作用并不依赖于Wnt或平面极性通路的下游信号。Dishevelled向p53的前50个氨基酸（即反式激活结构域）发出信号。p53该区域内几个丝氨酸残基的磷酸化水平会因Dishevelled的激活而升高，这在一定程度上促成了p53的激活。丝裂原活化蛋白激酶（MAP）通路和E1B55k可能也参与了Dishevelled与p53之间的联系。我们的数据表明，存在一条从Dishevelled到p53的新信号通路。
