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Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury

The Hippo signaling pathway controls cell proliferation and tissue regeneration via its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The canonical pathway topology is characterized by sequential phosphorylation of kinases in the...

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Main Authors: Wehling, Lilija (Author) , Keegan, Liam (Author) , Fernández-Palanca, Paula (Author) , Hassan, Reham (Author) , Ghallab, Ahmed (Author) , Schmitt, Jennifer (Author) , Tang, Yingyue (Author) , Le Marois, Maxime (Author) , Rössler, Stephanie (Author) , Schirmacher, Peter (Author) , Kummer, Ursula (Author) , Hengstler, Jan G (Author) , Sahle, Sven (Author) , Breuhahn, Kai (Author)
Format: Article (Journal)
Language:English
Published: 18 October 2022
In: eLife
Year: 2022, Volume: 11, Pages: 1-28
ISSN:2050-084X
DOI:10.7554/eLife.78540
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7554/eLife.78540
Verlag, lizenzpflichtig, Volltext: https://elifesciences.org/articles/78540
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Author Notes:Lilija Wehling, Liam Keegan, Paula Fernández-Palanca, Reham Hassan, Ahmed Ghallab, Jennifer Schmitt, Yingyue Tang, Maxime Le Marois, Stephanie Roessler, Peter Schirmacher, Ursula Kummer, Jan G Hengstler, Sven Sahle, Kai Breuhahn
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Summary:The Hippo signaling pathway controls cell proliferation and tissue regeneration via its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The canonical pathway topology is characterized by sequential phosphorylation of kinases in the cytoplasm that defines the subcellular localization of YAP and TAZ. However, the molecular mechanisms controlling the nuclear/cytoplasmic shuttling dynamics of both factors under physiological and tissue-damaging conditions are poorly understood. By implementing experimental in vitro data, partial differential equation modeling, as well as automated image analysis, we demonstrate that nuclear phosphorylation contributes to differences between YAP and TAZ localization in the nucleus and cytoplasm.
Item Description:Gesehen am 14.12.2022
Physical Description:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.78540

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