NDLI: Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ)

Content Provider	Journal of Biological Chemistry (JBC)
Author	Gandhirajan, Rajesh Kumar Jain, Manaswita Walla, Benedikt Johnsen, Marc Bartram, Malte P. Anh, Minh Huynh Rinschen, Markus M. Benzing, Thomas Schermer, Bernhard
Abstract	Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) are critical transcriptional co-activators downstream of the Hippo pathway involved in the regulation of organ size, tissue regeneration, proliferation, and apoptosis. Recent studies suggested common and distinct functions of TAZ and YAP and their diverse impact under several pathological conditions. Here we report differential regulation of TAZ and YAP in response to oxidative stress. H2O2 exposure leads to increased stability and activation of TAZ but not of YAP. H2O2 induces reversible S-glutathionylation at conserved cysteine residues within TAZ. We further demonstrate that TAZ S-glutathionylation is critical for reactive oxygen species (ROS)-mediated, TAZ-dependent TEA domain transcription factor (TEAD) trans-activation. Lysophosphatidic acid, a physiological activator of YAP and TAZ, induces ROS elevation and, subsequently, TAZ S-glutathionylation, which promotes TAZ-mediated target gene expression. TAZ expression is essential for renal homeostasis in mice, and we identify basal TAZ S-glutathionylation in murine kidney lysates, which is elevated during ischemia/reperfusion injury in vivo. This induced nuclear localization of TAZ and increased expression of connective tissue growth factor. These results describe a novel mechanism by which ROS sustains total cellular levels of TAZ. This preferential regulation suggests TAZ to be a redox sensor of the Hippo pathway.
Related Links	http://www.jbc.org/content/291/22/11596.abstract
Ending Page	11607
Starting Page	11596
Page Count	12
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	22
Volume Number	291
DOI	10.1074/jbc.M115.712539
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2016-05-27
Access Restriction	Open
Subject Keyword	Connective tissue growth factor (CTGF) Hippo pathway Oxidative stress Reactive oxygen species (ROS) Yes-associated protein (YAP) S-glutathionylation Transcriptional co-activator with PDZ-binding motif (TAZ) Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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