title: Several human PATCHED1 mutations block protein maturation.
abstract: The tumor suppressor gene PATCHED1 (PTCH1) is mutated in sporadic and inherited forms of basal cell carcinoma. PTCH1 binds Hedgehog proteins and inhibits signaling in the absence of ligand. Although PTCH1 mutations are proposed to reduce or abolish protein function, few mutations have been tested for activity. We introduced six PTCH1 missense mutations into mouse patched1 and tested them in murine cells deficient for patched1 function. Three mutants retained significant activity. Three other mutants had little or no function, and of these, two were retained in the secretory pathway. These studies indicate that missense mutations can abolish PTCH1 function by blocking protein maturation.
authors.affiliation: Departments of Cell Biology and Neurobiology, University of Alabama at Birmingham, Alabama 35294-0005, USA.
authors.forename: Evans C
authors.initials: EC
authors.lastname: Bailey
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D007763:Lac Operon / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface