Disease relevance of Perp

• We find that mice lacking Perp in the skin are resistant to papilloma development, displaying fewer and smaller papillomas than wild-type mice [1].
• Adult mice lacking the p53/p63 target gene Perp are not predisposed to spontaneous tumorigenesis but display features of ectodermal dysplasia syndromes [2].
• However, it is unclear if these phenotypes are strictly related to Perp function in stratified epithelia, as Perp expression is not restricted to these tissues during embryogenesis, and certain desmosomal blistering diseases such as pemphigus vulgaris and pemphigus foliaceus have non-cell-intrinsic bases [3].

High impact information on Perp

• Perp is a p63-regulated gene essential for epithelial integrity [4].
• 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 [4].
• During embryogenesis, Perp is expressed in an epithelial pattern, and its expression depends on p63 [4].
• 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 [4].
• Perp is a target of the p53 tumor suppressor involved in the DNA damage-induced apoptosis pathway [1].

Biological context of Perp

• Perp is a proapoptotic target gene of p53 expressed to high levels in apoptotic cells compared with those undergoing cell cycle arrest [5].
• Multiple response elements and differential p53 binding control Perp expression during apoptosis [5].
• Perp is a direct p53 target, and its overexpression is sufficient to induce cell death in fibroblasts, implicating it as an important component of p53 apoptotic function [6].

References