A Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53
Ju‐Gyeong Kang, Cory U. Lago, Ji‐Eun Lee, Jihoon Park, Matthew P. Donnelly, Matthew F. Starost, Chengyu Liu, Jaeyul Kwon, Audrey Noguchi, Kai Ge, Pingyuan Wang, Paul M. Hwang
Abstract
mice show a modest increase in tumorigenesis but, surprisingly, are lean with decreased body fat content. They display evidence of increased lipolysis and upregulation of fatty acid metabolism in their inguinal white adipose tissue (iWAT). Gene expression and chromatin immunoprecipitation sequencing (ChIP-seq) analyses show that the mutant p53 bound and transactivated Beta-3-Adrenergic Receptor (ADRB3), a gene that is known to promote lipolysis and is associated with obesity. This study reveals that a germline mutation of p53 can affect fat metabolism, which has been implicated in cancer development.