Universität zu Köln

Gandhirajan, Rajesh Kumar, Jain, Manaswita ORCID: 0000-0002-5107-7505, Walla, Benedikt, Johnsen, Marc, Bartram, Malte P., Rinschen, Markus M., Benzing, Thomas and Schermer, Bernhard ORCID: 0000-0002-5194-9000 (2016). Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ). J. Biol. Chem., 291 (22). S. 11596 - 11608. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gandhirajan, Rajesh Kumar UNSPECIFIED UNSPECIFIED UNSPECIFIED Jain, Manaswita UNSPECIFIED orcid.org/0000-0002-5107-7505 UNSPECIFIED Walla, Benedikt UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnsen, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartram, Malte P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rinschen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-275176
DOI:	10.1074/jbc.M115.712539
Journal or Publication Title:	J. Biol. Chem.
Volume:	291
Number:	22
Page Range:	S. 11596 - 11608
Date:	2016
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIAL-MESENCHYMAL TRANSITION; OXYGEN SPECIES GENERATION; REACTIVE OXYGEN; OXIDATIVE-STRESS; KIDNEY-DISEASE; CANCER CELLS; REPERFUSION INJURY; PATHWAY; PROTEIN; BETA Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27517