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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
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Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control
Yavuz Kulaberoglu1,2, Kui Lin3, Maxine Holder4
1Tumour Suppressor Signalling Network Laboratory, UCL Cancer Institute, University College London, London, WC1E 6BT, UK.
Nature Communications
|September 27, 2017
Summary
The Hippo pathway controls tissue growth and development. MOB1 binding to Warts kinase is crucial for tumor suppression, while binding to Hippo or Tricornered kinases is less important.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The Hippo pathway, comprising Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases and MOB1 adaptor, regulates tissue growth and suppresses tumors.
- The specific roles of MOB1 interactions with different Hippo core kinases in development and tumor suppression are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms by which MOB1 interacts with Hippo core kinases.
- To determine the functional significance of differential MOB1 binding to Hippo kinases in development, tissue growth, and tumor suppression.
Main Methods:
- Crystal structure determination of the MOB1/NDR2 complex.
- Generation and functional analysis of MOB1 variants with selective binding defects.
- In vitro and in vivo studies using human cancer cells and Drosophila models.
Main Results:
- Key MOB1 residues mediating differential binding to Hippo kinases were identified.
- MOB1/Warts kinase interaction is essential for tumor suppression, tissue growth control, and development.
- MOB1/Hippo kinase binding is dispensable, and MOB1/Tricornered kinase binding alone is insufficient for these processes.
Conclusions:
- The diverse interactions between Hippo core kinases and MOB1 are critical for precise regulation of development, tissue growth, and tumor suppression.
- MOB1's interaction with Warts kinase plays a pivotal role in Hippo pathway signaling.
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