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14-3-3 and ?-catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway.

ABSTRACT: Aberrant activation of the canonical Wnt signal transduction pathway is involved in a large number of human diseases. ?-catenin, the key effector protein of the canonical Wnt pathway, functions in the nucleus with T-cell factor/lymphoid enhancer factor (TCF/LEF) to activate expression of Wnt target genes. Here we show that members of the 14-3-3 protein family bind disheveled-2 (Dvl-2) and glycogen synthase-3? (GSK-3?) to attenuate the interaction between GSK-3? and ?-catenin. Importantly, 14-3-3 and ?-catenin form "bleb-like" structures and are secreted via extracellular vesicles to induce Wnt signaling activity in target cells. Our data suggest a novel way of transducing the oncogenic Wnt signal in which ?-catenin is regulated by 14-3-3? through the formation of "oncosomes" that contain both the 14-3-3 and ?-catenin proteins.

SUBMITTER: Dovrat S

PROVIDER: S-EPMC5528515 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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14-3-3 and β-catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway.

Dovrat Shiri S Caspi Michal M Zilberberg Alona A Lahav Lital L Firsow Anastasia A Gur Hila H Rosin-Arbesfeld Rina R

Molecular oncology 20140322 5

Aberrant activation of the canonical Wnt signal transduction pathway is involved in a large number of human diseases. β-catenin, the key effector protein of the canonical Wnt pathway, functions in the nucleus with T-cell factor/lymphoid enhancer factor (TCF/LEF) to activate expression of Wnt target genes. Here we show that members of the 14-3-3 protein family bind disheveled-2 (Dvl-2) and glycogen synthase-3β (GSK-3β) to attenuate the interaction between GSK-3β and β-catenin. Importantly, 14-3-3 ...[more]

PMID: 24721736

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Dataset Information

14-3-3 and ?-catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway.

Publications

14-3-3 and β-catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway.

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