Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein

H. Y. Lin, Henry J. Michtalik, ShenLi Zhang, Thomas T. Andersen, Dee A. Van Riper, Kelvin K J A Davies, Gennady Ermak, Lisa M. Petti, Schuyler Nachod, Ananth V. Narayan, Nishant Bhatt, Dana R. Crawford

Research output: Contribution to journalArticle

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Abstract

DSCR1 (adapt78) is a stress-inducible gene and cytoprotectant. Its protein product, DSCR1 (Adapt78), also referred to as MCIP1, inhibits intracellular calcineurin, a phosphatase that mediates many cellular responses to calcium. Exposure of human U251 and HeLa cells to hydrogen peroxide led to a rapid hyperphosphorylation of DSCR1 (Adapt78). Inhibitor and agonist studies revealed that a broad range of kinases were not responsible for DSCR1 (Adapt78) hyperphosphorylation, including ERK1/2, although parallel activation of the latter was observed. Phosphorylation of both DSCR1 (Adapt78) and ERK1/2 was attenuated by inhibitors of tyrosine phosphatase, suggesting the common upstream involvement of tyrosine dephosphorylation. The hyperphosphorylation electrophoretic shift in DSCR1 (Adapt78) mobility was also observed with other oxidizing agents (peroxynitrite and menadione) but not nonoxidants. Calcium ionophores strongly induced the levels of both hypo- and hyper-phosphorylated DSCR1 (Adapt78) but did not alter phosphorylation status. Calcium-dependent growth factor- and angiotensin II-stimulation also induced both DSCR1 (Adapt78) species. Phosphorylation of either or both serines in a 13-amino acid peptide made to a calcineurin-interacting conserved region of DSCR1 (Adapt78) attenuated inhibition of calcineurin. These data indicate that DSCR1 (Adapt78) protein is a novel, early stage oxidative stress-activated phosphorylation target and newly identified calcium-inducible protein, and suggest that these response mechanisms may contribute to the known cytoprotective and calcineurin-inhibitory activities of DSCR1 (Adapt78).

Original languageEnglish
Pages (from-to)528-539
Number of pages12
JournalFree Radical Biology and Medicine
Volume35
Issue number5
DOIs
Publication statusPublished - Sep 1 2003
Externally publishedYes

Fingerprint

Phosphorylation
Calcineurin
Oxidative Stress
Calcium
Phosphoric Monoester Hydrolases
Tyrosine
Proteins
Vitamin K 3
Peroxynitrous Acid
Oxidative stress
Calcium Ionophores
Prothrombin
HeLa Cells
Oxidants
Angiotensin II
Serine
Hydrogen Peroxide
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Genes

Keywords

  • Calcineurin
  • Calcium-inducible
  • Free radicals
  • Oxidative stress
  • Stress response

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Lin, H. Y., Michtalik, H. J., Zhang, S., Andersen, T. T., Van Riper, D. A., Davies, K. K. J. A., ... Crawford, D. R. (2003). Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. Free Radical Biology and Medicine, 35(5), 528-539. https://doi.org/10.1016/S0891-5849(03)00358-7

Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. / Lin, H. Y.; Michtalik, Henry J.; Zhang, ShenLi; Andersen, Thomas T.; Van Riper, Dee A.; Davies, Kelvin K J A; Ermak, Gennady; Petti, Lisa M.; Nachod, Schuyler; Narayan, Ananth V.; Bhatt, Nishant; Crawford, Dana R.

In: Free Radical Biology and Medicine, Vol. 35, No. 5, 01.09.2003, p. 528-539.

Research output: Contribution to journalArticle

Lin, HY, Michtalik, HJ, Zhang, S, Andersen, TT, Van Riper, DA, Davies, KKJA, Ermak, G, Petti, LM, Nachod, S, Narayan, AV, Bhatt, N & Crawford, DR 2003, 'Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein', Free Radical Biology and Medicine, vol. 35, no. 5, pp. 528-539. https://doi.org/10.1016/S0891-5849(03)00358-7
Lin HY, Michtalik HJ, Zhang S, Andersen TT, Van Riper DA, Davies KKJA et al. Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. Free Radical Biology and Medicine. 2003 Sep 1;35(5):528-539. https://doi.org/10.1016/S0891-5849(03)00358-7
Lin, H. Y. ; Michtalik, Henry J. ; Zhang, ShenLi ; Andersen, Thomas T. ; Van Riper, Dee A. ; Davies, Kelvin K J A ; Ermak, Gennady ; Petti, Lisa M. ; Nachod, Schuyler ; Narayan, Ananth V. ; Bhatt, Nishant ; Crawford, Dana R. / Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. In: Free Radical Biology and Medicine. 2003 ; Vol. 35, No. 5. pp. 528-539.
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