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All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and
Tsutomu Oka1, Eline Remue, Kris Meerschaert
1Weis Center for Research, 100 North Academy Avenue, Danville, PA 17822, USA.
The Biochemical Journal
|September 28, 2010
Summary
The zonula occludens (ZO)-2 protein binds to Yes kinase-associated protein 2 (YAP2), facilitating its nuclear entry and promoting apoptosis. This YAP2-ZO-2 complex offers a potential target for cancer therapies.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- The Hippo pathway is crucial for organ size regulation, controlling cell proliferation and apoptosis.
- Yes kinase-associated protein 2 (YAP2) is a key effector of the Hippo pathway, acting as a transcriptional co-activator.
- YAP2 contains WW domains and a C-terminal PDZ-binding motif, previously shown to be vital for nuclear localization and apoptosis induction.
Purpose of the Study:
- To investigate the interaction between YAP2 and the tight junction protein zonula occludens (ZO)-2.
- To elucidate the role of ZO-2 in YAP2's nuclear localization and function.
- To explore the potential of the YAP2-ZO-2 complex as a cancer therapeutic target.
Main Methods:
- Co-immunoprecipitation assays to detect protein complex formation.
- Immunofluorescence microscopy to assess protein co-localization.
- Functional assays to evaluate the impact of ZO-2 on YAP2's pro-apoptotic activity.
Main Results:
- The tight junction protein ZO-2 directly binds to YAP2 via its PDZ domain.
- Endogenous ZO-2 and YAP2 proteins co-localize within the nucleus.
- ZO-2 enhances YAP2's nuclear translocation and pro-apoptotic function in a PDZ-domain-dependent manner.
Conclusions:
- This study reveals a novel PDZ-domain-based mechanism for nuclear translocation of YAP2 mediated by ZO-2.
- The interaction between YAP2 and ZO-2 is essential for YAP2's pro-apoptotic activity.
- The YAP2-ZO-2 complex represents a promising target for developing novel cancer therapies, given the Hippo pathway's tumor suppressor role.
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