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 language | English |
|---|---|
| Pages (from-to) | 528-539 |
| Number of pages | 12 |
| Journal | Free Radical Biology and Medicine |
| Volume | 35 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 1 2003 |
| Externally published | Yes |
Fingerprint
Keywords
- Calcineurin
- Calcium-inducible
- Free radicals
- Oxidative stress
- Stress response
ASJC Scopus subject areas
- Medicine(all)
- Toxicology
- Clinical Biochemistry
Cite this
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 journal › Article
}
TY - JOUR
T1 - Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein
AU - Lin, H. Y.
AU - Michtalik, Henry J.
AU - Zhang, ShenLi
AU - Andersen, Thomas T.
AU - Van Riper, Dee A.
AU - Davies, Kelvin K J A
AU - Ermak, Gennady
AU - Petti, Lisa M.
AU - Nachod, Schuyler
AU - Narayan, Ananth V.
AU - Bhatt, Nishant
AU - Crawford, Dana R.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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).
AB - 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).
KW - Calcineurin
KW - Calcium-inducible
KW - Free radicals
KW - Oxidative stress
KW - Stress response
UR - http://www.scopus.com/inward/record.url?scp=10744226066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744226066&partnerID=8YFLogxK
U2 - 10.1016/S0891-5849(03)00358-7
DO - 10.1016/S0891-5849(03)00358-7
M3 - Article
C2 - 12927602
AN - SCOPUS:10744226066
VL - 35
SP - 528
EP - 539
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 5
ER -