Article
Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.
Cancer cell - 1 Oct 2007
Itahana Koji, Mao Hua, Jin Aiwen, Itahana Yoko, Clegg Hilary V, Lindström Mikael S, Bhat Krishna P, Godfrey Virginia L, Evan Gerard I, Zhang Yanping
Abstract excerpt
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....
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