| First Author | Itahana K | Year | 2007 |
| Journal | Cancer Cell | Volume | 12 |
| Issue | 4 | Pages | 355-66 |
| PubMed ID | 17936560 | Mgi Jnum | J:126004 |
| Mgi Id | MGI:3760347 | Doi | 10.1016/j.ccr.2007.09.007 |
| Citation | Itahana K, et al. (2007) Targeted Inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell 12(4):355-66 |
| abstractText | It is believed that Mdm2 suppresses p53 in two ways: transcriptional inhibition by direct binding, and degradation via its E3 ligase activity. To study these functions physiologically, we generated mice bearing a single-residue substitution (C462A) abolishing the E3 function without affecting p53 binding. Unexpectedly, homozygous mutant mice died before E7.5, and deletion of p53 rescued the lethality. Furthermore, reintroducing a switchable p53 by crossing with p53ER(TAM) mice surprisingly demonstrated that the mutant Mdm2(C462A) was rapidly degraded in a manner indistinguishable from that of the wild-type Mdm2. Hence, our data indicate that (1) the Mdm2-p53 physical interaction, without Mdm2-mediated p53 ubiquitination, cannot control p53 activity sufficiently to allow early mouse embryonic development, and (2) Mdm2's E3 function is not required for Mdm2 degradation. |
