First Author | Sanford JD | Year | 2023 |
Journal | Cell Rep | Volume | 42 |
Issue | 1 | Pages | 111920 |
PubMed ID | 36640361 | Mgi Jnum | J:340332 |
Mgi Id | MGI:7434096 | Doi | 10.1016/j.celrep.2022.111920 |
Citation | Sanford JD, et al. (2023) A role of cytoplasmic p53 in the regulation of metabolism shown by bat-mimicking p53 NLS mutant mice. Cell Rep 42(1):111920 |
abstractText | The transcription factor p53 suppresses tumorigenesis via a wide-ranging, concerted set of functions. Although several studies have identified cytoplasmic, transcription-independent functions of p53, the biological relevance of these activities has not been fully elucidated, particularly in vivo. Here, we generated a mouse model with a p53(K316P) mutation, which mimics a naturally occurring p53 nuclear localization signal (NLS) change observed in bat species. We find that the p53(K316P) mutation increases cytoplasmic localization of p53 and promotes a pleiotropic metabolic phenotype that includes increased adiposity, increased de novo lipogenesis, and decreased lactate generation. Mechanistic studies show that, independent of its transactivation function, p53(K316P) interacts with lactate dehydrogenase B (LDHB) and alters the composition and enzymatic activities of LDH complex favoring pyruvate generation and hindering lactate production. Overall, the study identifies a role for cytoplasmic p53 in the regulation of metabolism that favors energy generation and storage. |