Redox response of the endogenous calcineurin inhibitor Adapt78

Ananth V. Narayan, Rebecca Stadel, Amy B. Hahn, Dipti L. Bhoiwala, Geysha Cornielle, Erwin Sarazin, Issam Koleilat, Dana R. Crawford

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Adapt78 (DSCR1/calcipressin/MCIP1) is a potent natural inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. We previously reported two major cytosolic isoforms (1 and 4) of Adapt78, and that isoform 4 is an oxidative and calcium stress-response protein. Using a higher cell culture density and new antibody, we again observed that both major isoforms localized to the cytosol, but a significant level of isoform 4 (but not isoform 1) was also detected in the nucleus where it was present in the nonsoluble region and not associated with RNA. Exposure of cells to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus with a moderate increase in cytosolic localization. The change in isoform 4 phosphorylation state in response to oxidative stress, characterized by a loss of the lesser (hypo) phosphorylated Adapt78, was not due to accelerated degradation, although general Adapt78 degradation was proteosome mediated. Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform 4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine inhibitable, and accompanied by induction of the classic immune response mediator and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox-related activities for Adapt78 isoform 4, which may contribute to its known calcineurin-regulating and cytoprotective activities, and further suggest that Adapt78 plays a role in basic T-cell response.

Original languageEnglish (US)
Pages (from-to)719-727
Number of pages9
JournalFree Radical Biology and Medicine
Volume39
Issue number6
DOIs
Publication statusPublished - Sep 15 2005
Externally publishedYes

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Keywords

  • Calcineurin
  • Free radicals
  • Hydrogen peroxide
  • Oxidative stress
  • Redox
  • Stress-response
  • Subcellular localization
  • T-cell response

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Narayan, A. V., Stadel, R., Hahn, A. B., Bhoiwala, D. L., Cornielle, G., Sarazin, E., ... Crawford, D. R. (2005). Redox response of the endogenous calcineurin inhibitor Adapt78. Free Radical Biology and Medicine, 39(6), 719-727. https://doi.org/10.1016/j.freeradbiomed.2005.03.036