EIF3H orchestrates Hippo pathway-mediated oncogenesis via catalytic control of YAP stability: EIF3H is presumed to be a critical translational initiation factor. Here our unbiased screening for tumor invasion factors has identified an unexpected role for EIF3H as a deubiquitylating enzyme that dictates breast tumor invasion and metastasis by modulating the Hippo-YAP pathway. EIF3H catalyzed YAP for deubiquitylation, resulting in its stabilization. Structure-based molecular modelling and simulations coupled with biochemical characterization unveiled a unique catalytic mechanism for EIF3H in dissociating polyubiquitin chains from YAP through a catalytic triad consisting of Asp90, Asp91, and Gln121. Trp119 and Tyr 140 on EIF3H directly interacted with the N-terminal region of YAP1, facilitating complex formation of EIF3H and YAP1 for YAP1 deubiquitylation. Stabilization of YAP via elevated EIF3H promoted tumor invasion and metastasis. Interference of EIF3H-mediated YAP deubiquitylation blocked YAP-induced tumor progression and metastasis in breast cancer models. These findings point to a critical role for YAP regulation by EIF3H in tumor invasion and metastasis.
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Τετάρτη 8 Απριλίου 2020
EIF3H orchestrates Hippo pathway-mediated oncogenesis via catalytic control of YAP stability
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
10:58 μ.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis,
Telephone consultation 11855 int 1193
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