Switch #: SWTI000682

Switch type: Avidity-sensing

Description:
Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage.

Participants:
(1) 14-3-3 protein zeta/delta (YWHAZ)
(2) Protein Mdm4 (MDM4)

This is a sequential switch. The interactions in this switch take place in a defined order. The order is defined by numbers to the left of each interaction. More than one interaction can occur in each step, these interactions occur independently but are necessary for future step

1Interaction #1 YWHAZ - YWHAZ

Interfaces
(1) 14-3-3 protein in 14-3-3 protein zeta/delta (YWHAZ)
(2) 14-3-3 protein _(3-236) in 14-3-3 protein zeta/delta (YWHAZ)

2Interaction #2 MDM4 - Interaction #1 YWHAZ - YWHAZ

Requires Interaction #1 YWHAZ - YWHAZ

Interfaces
(3) LIG_14-3-3_1 motif (₃₆₄RTISAP₃₆₉) in Protein Mdm4 (MDM4)
(4) Interaction #1 YWHAZ - YWHAZ

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₆₇ on Protein Mdm4 (MDM4)) of the Protein Mdm4 (MDM4) LIG_14-3-3_1 motif - 14-3-3 protein interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₃₆₇: Serine/threonine-protein kinase Chk2 (CHEK2)

2Interaction #3 MDM4 - Interaction #1 YWHAZ - YWHAZ

Requires Interaction #1 YWHAZ - YWHAZ

Interfaces
(5) LIG_14-3-3_3 motif (₃₃₉HSLSTS₃₄₄) in Protein Mdm4 (MDM4)
(6) Interaction #1 YWHAZ - YWHAZ

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₃₄₂ on Protein Mdm4 (MDM4)) of the Protein Mdm4 (MDM4) LIG_14-3-3_3 motif - 14-3-3 protein interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₃₄₂: Serine/threonine-protein kinase Chk2 (CHEK2)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₃₄₂ : Serine/threonine-protein kinase Chk1 (CHEK1), Serine/threonine-protein kinase Chk2 (CHEK2).

(1) Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage.
Pereg et al. Mol. Cell. Biol. (2006)

Other switches involving participants
14-3-3 protein zeta/delta (YWHAZ) - 11 more (view)
Protein Mdm4 (MDM4) - 1 more (view)

Other switches involving interfaces
14-3-3 protein - 38 more (view)
LIG_14-3-3_3 - 16 more (view)
LIG_14-3-3_1 - 13 more (view)