由p53转录激活的PTCH1同源物抑制Hedgehog信号通路。
A PTCH1 homolog transcriptionally activated by p53 suppresses Hedgehog signaling.
作者信息
Chung Jon H, Larsen Andrew R, Chen Evan, Bunz Fred
机构信息
From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231.
From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231
出版信息
J Biol Chem. 2014 Nov 21;289(47):33020-31. doi: 10.1074/jbc.M114.597203. Epub 2014 Oct 8.
Abstract
The p53-mediated responses to DNA damage and the Hedgehog (Hh) signaling pathway are each recurrently dysregulated in many types of human cancer. Here we describe PTCH53, a p53 target gene that is homologous to the tumor suppressor gene PTCH1 and can function as a repressor of Hh pathway activation. PTCH53 (previously designated PTCHD4) was highly responsive to p53 in vitro and was among a small number of genes that were consistently expressed at reduced levels in diverse TP53 mutant cell lines and human tumors. Increased expression of PTCH53 inhibited canonical Hh signaling by the G protein-coupled receptor SMO. PTCH53 thus delineates a novel, inducible pathway by which p53 can repress tumorigenic Hh signals.
摘要
p53介导的对DNA损伤的反应和刺猬（Hh）信号通路在许多类型的人类癌症中均反复出现失调。在此，我们描述了PTCH53，这是一个与肿瘤抑制基因PTCH1同源的p53靶基因，可作为Hh通路激活的抑制剂。PTCH53（以前称为PTCHD4）在体外对p53高度敏感，并且是在多种TP53突变细胞系和人类肿瘤中持续表达水平降低的少数基因之一。PTCH53的表达增加通过G蛋白偶联受体SMO抑制经典Hh信号传导。因此，PTCH53描绘了一条新的、可诱导的途径，通过该途径p53可以抑制致癌性Hh信号。
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