Switch #: SWTI000681

Switch type: Binary

Switch subtype: Physicochemical compatibility

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)

Other switches involving participants
Ubiquitin carboxyl-terminal hydrolase 7 (USP7) - 2 more (view)
Protein Mdm4 (MDM4) - 1 more (view)

Other switches involving interfaces
DOC_USP7_1 - 2 more (view)
MATH domain - 1 more (view)