title: Perp is a p63-regulated gene essential for epithelial integrity.
abstract: p63 is a master regulator of stratified epithelial development that is both necessary and sufficient for specifying this multifaceted program. We show here that Perp, a tetraspan membrane protein originally identified as an apoptosis-associated target of the p53 tumor suppressor, is the first direct target of p63 clearly involved in mediating this developmental program in vivo. During embryogenesis, Perp is expressed in an epithelial pattern, and its expression depends on p63. Perp-/- mice die postnatally, with dramatic blistering in stratified epithelia symptomatic of compromised adhesion. Perp localizes specifically to desmosomes, adhesion junctions important for tissue integrity, and numerous structural defects in desmosomes are observed in Perp-deficient skin, suggesting a role for Perp in promoting the stable assembly of desmosomal adhesive complexes. These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis.
authors.affiliation: Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Ihrie
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Marques
authors.forename: Bichchau T
authors.initials: BT
authors.lastname: Nguyen
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Horner
authors.forename: Cristian
authors.initials: C
authors.lastname: Papazoglu
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Alea A
authors.initials: AA
authors.lastname: Mills
authors.forename: Laura D
authors.initials: LD
authors.lastname: Attardi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D047109:Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D008565:Membrane Proteins; C406964:Perp protein, mouse; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse