| First Author | Kon N | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 7 | Pages | 5102-11 |
| PubMed ID | 22187431 | Mgi Jnum | J:182446 |
| Mgi Id | MGI:5315649 | Doi | 10.1074/jbc.M111.322867 |
| Citation | Kon N, et al. (2012) Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice. J Biol Chem 287(7):5102-11 |
| abstractText | It is well accepted that the Mdm2 ubiquitin ligase acts as a major factor in controlling p53 stability and activity in vivo. Although several E3 ligases have been reported to be involved in Mdm2-independent p53 degradation, the roles of these ligases in p53 regulation in vivo remain largely unknown. To elucidate the physiological role of the ubiquitin ligase ARF-BP1, we generated arf-bp1 mutant mice. We found that inactivation of arf-bp1 during embryonic development in mice resulted in p53 activation and embryonic lethality, but the mice with arf-bp1 deletion specifically in the pancreatic beta-cells (arf-bp1(FL/Y)/RIP-cre) were viable and displayed no obvious abnormality after birth. Interestingly, these mice showed dramatic loss of beta-cells as mice aged, and >50% of these mice died of severe diabetic symptoms before reaching 1 year of age. Notably, the diabetic phenotype of these mice was largely reversed by concomitant deletion of p53, and the life span of the mice was significantly extended (p53(LFL/FL)/arf-bp1(FL/Y)/RIP-cre). These findings underscore an important role of ARF-BP1 in maintaining beta-cell homeostasis in aging mice and reveal that the stability of p53 is critically regulated by ARF-BP1 in vivo. |
