title: TAZ suppresses NFAT5 activity through tyrosine phosphorylation.
abstract: Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple renal cysts and urinary concentration defects; however, the molecular functions of TAZ in renal cells remain largely unknown. In this study, we examined the effects of osmotic stress on TAZ expression and activity in renal cells. We found that hyperosmotic stress selectively increased protein phosphorylation at tyrosine 316 of TAZ and that this was enhanced by c-Abl activation in response to hyperosmotic stress. Interestingly, phosphorylated TAZ physically interacted with nuclear factor of activated T cells 5 (NFAT5), a major osmoregulatory transcription factor, and subsequently suppressed DNA binding and transcriptional activity of NFAT5. Furthermore, TAZ deficiency elicited an increase in NFAT5 activity in vitro and in vivo, which then reverted to basal levels following restoration of wild-type TAZ but not mutant TAZ (Y316F). Collectively, the data suggest that TAZ modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation.
authors.affiliation: College of Pharmacy, Division of Life and Pharmaceutical Sciences, and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Republic of Korea. eshwang@ewha.ac.kr
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Jang
authors.forename: Hana
authors.initials: H
authors.lastname: Jeong
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Han
authors.forename: Hyug Moo
authors.initials: HM
authors.lastname: Kwon
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009997:Osmotic Pressure; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D050505:Mutant Proteins; C492200:Nfat5 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors; D014443:Tyrosine; D004247:DNA; D000217:Acyltransferases; C486363:tafazzin protein, mouse; D016315:Proto-Oncogene Proteins c-abl