Abstract
The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ. To provide an overview of important Hippo pathway components, we created knockout cell lines for many of these components and compared their relative contributions to YAP/TAZ regulation in response to a wide range of physiological signals. By this approach, we provide an overview of the functional importance of many Hippo pathway components and demonstrate NF2 and RHOA as important regulators of YAP/TAZ and TAOK1/3 as direct kinases for LATS1/2.
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•Comparing knockouts enables us to identify the most important regulators of YAP/TAZ•Deletion of NF2 or RHOA results in significant disruption of YAP/TAZ regulation•TAOK1/3 are direct kinases for LATS1/2
Plouffe et al. created knockout cell lines of many Hippo pathway components to identify which are most physiologically relevant in regulating YAP/TAZ. Deletion of NF2 or RHOA results in significant disruption of YAP/TAZ, and TAOK1/3 are direct kinases for LATS1/2.
