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Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control

Kulaberoglu, Y; Lin, K; Holder, M; Gai, Z; Gomez, M; Shifa, BA; Mavis, M; ... Hergovich, A; + view all (2017) Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control. Nature Communications , 8 , Article 695. 10.1038/s41467-017-00795-y. Green open access

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Abstract

The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1’s differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.

Type: Article
Title: Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-017-00795-y
Publisher version: http://dx.doi.org/10.1038/s41467-017-00795-y
Additional information: Open Acces: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, HUMAN NDR KINASES, TUMOR-SUPPRESSOR, CELL-PROLIFERATION, PROMOTES APOPTOSIS, STRUCTURAL BASIS, PROTEIN-KINASE, PATHWAY, DROSOPHILA, ACTIVATION, FAMILY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10024325
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