Regulation of the hypertonic stress response and other cellular functions by the Rel-like transcription factor NFAT5.
Stress, be it from environmental factors or intrinsic to the cell as result of growth and metabolism, can be harmful to cells. Mammalian cells have developed numerous mechanisms to respond to diverse forms of stress. These mechanisms combine signaling cascades and activation of gene expression programs to orchestrate an adaptive response that will allow the cell to survive and resume its normal functioning. In this review we will focus on the transcription factor NFAT5, a fundamental regulator of the response to osmotic stress in mammalian cells. Identified in 1999, NFAT5 is the latest addition to the Rel family, which comprises the NF-kappaB and NFATc proteins. Though in some of its structural and functional features NFAT5 is a hybrid between these two major groups of Rel proteins, it has unique characteristics that make it stand on its own as a third type of Rel transcription factor. Since its discovery, NFAT5 has been studied mostly in the context of the hypertonicity stress response. The advent of mouse models deficient in NFAT5 and other recent advances have confirmed a fundamental osmoprotective role for this factor in mammals, but also revealed features that suggest it may have a wider range of functions.
Aramburu
José
J
Molecular Immunopathology Unit, Department of Experimental and Health Sciences (DCEXS), Universitat Pompeu Fabra, Carrer Dr. Aiguader 80, E-08003 Barcelona, Spain. jose.aramburu@upf.edu
Drews-Elger
Katherine
K
Estrada-Gelonch
Anaïs
A
Minguillón
Jordi
J
Morancho
Beatriz
B
Santiago
Verónica
V
López-Rodríguez
Cristina
C
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009997:Osmotic Pressure; D016415:Sequence Alignment; D051841:Transcription Factor RelB / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C118125:NFAT5 protein, human; D050778:NFATC Transcription Factors; D014157:Transcription Factors; D051841:Transcription Factor RelB