Proteomics

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Wnt Regulation: Exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex


ABSTRACT: Wnt signaling plays key roles in development and disease, by regulating the stability of its key effector βcat. In the absence of Wnt signals, βcat is phosphorylated by the Wnt-regulatory destruction complex, ubiquitinated by an SCF-class E3 ubiquitin ligase, and destroyed by the proteasome. Binding of Wnt ligands to their Frizzled/LRP receptors stabilizes βcat, via the cytoplasmic effector Dsh. Here we explore two important questions in the field: Is there a direct transfer of βcat from the destruction complex to the E3 ligase, and how does Dsh interaction with the destruction complex protein Axin regulate destruction complex function?

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Kidney

SUBMITTER: Dennis Goldfarb  

LAB HEAD: Mark Peifer

PROVIDER: PXD016314 | Pride | 2020-04-20

REPOSITORIES: Pride

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Publications

Wnt regulation: exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex.

Schaefer Kristina N KN   Pronobis Mira I MI   Williams Clara E CE   Zhang Shiping S   Bauer Lauren L   Goldfarb Dennis D   Yan Feng F   Major M Ben MB   Peifer Mark M  

Molecular biology of the cell 20200304 10


Wnt signaling plays key roles in embryonic development and adult stem cell homeostasis and is altered in human cancer. Signaling is turned on and off by regulating stability of the effector β-catenin (β-cat). The multiprotein destruction complex binds and phosphorylates β-cat and transfers it to the SCF-TrCP E3-ubiquitin ligase for ubiquitination and destruction. Wnt signals act though Dishevelled to turn down the destruction complex, stabilizing β-cat. Recent work clarified underlying mechanism  ...[more]

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