title: A PTCH1 homolog transcriptionally activated by p53 suppresses Hedgehog signaling.
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.
authors.affiliation: From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231.
authors.forename: Jon H
authors.initials: JH
authors.lastname: Chung
authors.affiliation: From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Larsen
authors.affiliation: From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231.
authors.forename: Evan
authors.initials: E
authors.lastname: Chen
authors.affiliation: From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 fredbunz@jhmi.edu.
authors.forename: Fred
authors.initials: F
authors.lastname: Bunz
mesh_terms: D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D045325:HCT116 Cells; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C000595194:PTCHD4 protein, human; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53
keywords: DNA Damage Response; Sonic Hedgehog (SHH); Tumor Cell Biology; Tumor Suppressor Gene; p53