Switch #: SWTI000295

Switch type: Specificity

Switch subtype: Altered binding specificity

Description:
Phosphorylation of SREBP-1 (Sterol regulatory element-binding protein 1 (SREBF1)) at S430 generates a docking site for Glycogen synthase kinase-3 beta (GSK3B). Subsequent phosphorylation of SREBP-1 (SREBF1) by GSK3B at T426 switches the specificity of SREBP-1 (SREBF1) to the F-box/WD repeat-containing protein 7 (FBXW7), which recruits SREBP-1 (SREBF1) to the SCF ubiquitin ligase complex to mark SREBP-1 (SREBF1) for degradation.

Participants:
(1) Sterol regulatory element-binding protein 1 (SREBF1)
(2) Glycogen synthase kinase-3 beta (GSK3B)
(3) F-box/WD repeat-containing protein 7 (FBXW7)

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 SREBF1 - GSK3B

Is mutually exclusive with Interaction #2 SREBF1 - FBXW7

Interfaces
(1) MOD_GSK3_1 motif (₄₂₂EDTLTPPPS₄₃₀) in Sterol regulatory element-binding protein 1 (SREBF1)
(2) Protein kinase domain _(56-340) in Glycogen synthase kinase-3 beta (GSK3B)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₄₃₀ on Sterol regulatory element-binding protein 1 (SREBF1)) of the Sterol regulatory element-binding protein 1 (SREBF1) MOD_GSK3_1 motif - Glycogen synthase kinase-3 beta (GSK3B) Protein kinase domain interaction

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₄₃₀ : Glycogen synthase kinase-3 beta (GSK3B).

2Interaction #2 SREBF1 - FBXW7

Requires Interaction #1 SREBF1 - GSK3B
Is mutually exclusive with Interaction #1 SREBF1 - GSK3B

Interfaces
(3) DEG_SCF_FBW7_1 motif (₄₂₅LTPPPS₄₃₀) in Sterol regulatory element-binding protein 1 (SREBF1)
(4) WD domain, G-beta repeat _(371-407) and _(411-447) and _(451-487) and _(491-527) and _(531-567) and _(571-607) and _(611-650) in F-box/WD repeat-containing protein 7 (FBXW7)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T₄₂₆ and S₄₃₀ on Sterol regulatory element-binding protein 1 (SREBF1)) of the Sterol regulatory element-binding protein 1 (SREBF1) DEG_SCF_FBW7_1 motif - F-box/WD repeat-containing protein 7 (FBXW7) WD domain, G-beta repeat interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: T₄₂₆: Glycogen synthase kinase-3 beta (GSK3B)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: T₄₂₆ : Glycogen synthase kinase-3 beta (GSK3B). S₄₃₀ : Glycogen synthase kinase-3 beta (GSK3B).

(1) Phosphorylation and ubiquitination of the transcription factor sterol regulatory element-binding protein-1 in response to DNA binding.
Punga et al. J. Biol. Chem. (2006)

(2) Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7).
Sundqvist et al. Cell Metab. (2005)