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Expanded directly binds conserved regions of Fat to restrain growth via the Hippo pathway

J Cell Biol. 2023-04; 
Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen McNeill
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Peptide Synthesis … N-terminally biotin-tagged Ft peptide was generated by GenScript. 100 pmol purified GST-protein, 10 μg biotin-peptide, or 10 μl FLAG-tagged TnT T7 product was incubated with 10 μl … Get A Quote

摘要

The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes loss of apical Expanded and promotes tissue overgr... More

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