Description: Phosphorylation of S403 adjacent to the USP7-binding motif of Protein Mdm4 (MDM4) by Serine-protein kinase ATM (ATM) inhibits binding to the Ubiquitin carboxyl-terminal hydrolase 7 (USP7), thereby reducing deubiquitylation of Protein Mdm4 (MDM4). As a result, ubiquitylation by E3 ubiquitin-protein ligase Mdm2 (MDM2) is not countered and Protein Mdm4 (MDM4) is targeted for proteasomal degradation.
Participants: (1) Protein Mdm4 (MDM4) (2) Ubiquitin carboxyl-terminal hydrolase 7 (USP7)
(1) Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2.Meulmeester et al. Mol. Cell (2005) (2) Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage.Pereg et al. Proc. Natl. Acad. Sci. U.S.A. (2005) (3) ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage.Chen et al. EMBO J. (2005)
