AI Article Synopsis

  • - NFAT5 is a transcription factor that helps cells protect themselves from hypertonicity by promoting the production of protective organic osmolytes through gene transcription.
  • - Research shows that the N-terminal domain (NTD) of NFAT5 can sense changes in osmolytes and hypertonicity, leading to a stabilizing structural change that enhances its function.
  • - This structural change in NFAT5 allows it to interact with other proteins, potentially increasing cell survival under stress conditions by preventing apoptosis.

Article Abstract

Nuclear Factor of Activated T cells 5 (NFAT5) is a transcription factor (TF) that mediates protection from adverse effects of hypertonicity by increasing transcription of genes, including those that lead to cellular accumulation of protective organic osmolytes. NFAT5 has three intrinsically ordered (ID) activation domains (ADs). Using the NFAT5 N-terminal domain (NTD), which contains AD1, as a model, we demonstrate by biophysical methods that the NTD senses osmolytes and hypertonicity, resulting in stabilization of its ID regions. In the presence of sufficient NaCl or osmolytes, trehalose and sorbitol, the NFAT5 NTD undergoes a disorder-to-order shift, adopting higher average secondary and tertiary structure. Thus, NFAT5 is activated by the stress that it protects against. In its salt and/or osmolyte-induced more ordered conformation, the NTD interacts with several proteins, including HMGI-C, which is known to protect against apoptosis. These findings raise the possibility that the increased intracellular ionic strength and elevated osmolytes caused by hypertonicity activate and stabilize NFAT5.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443939PMC
http://dx.doi.org/10.1073/pnas.1911680117DOI Listing

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