2. Academic Validation
  3. A PTCH1 homolog transcriptionally activated by p53 suppresses Hedgehog signaling

A PTCH1 homolog transcriptionally activated by p53 suppresses Hedgehog signaling

  • J Biol Chem. 2014 Nov 21;289(47):33020-31. doi: 10.1074/jbc.M114.597203.
Jon H Chung 1,  Andrew R Larsen 1,  Evan Chen 1,  Fred Bunz 2
Affiliations

Affiliations

  • 1 From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231.
  • 2 From the Department of Radiation Oncology and Molecular Radiation Sciences, The Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 fredbunz@jhmi.edu.
PMID: 25296753 DOI: 10.1074/jbc.M114.597203
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.

Keywords

DNA Damage Response; Sonic Hedgehog (SHH); Tumor Cell Biology; Tumor Suppressor Gene; p53.

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