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Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin

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Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin. / Ho, Ka-Kei; McGuire, Victoria A.; Koo, Chuay-Yeng; Muir, Kyle W.; de Olano, Natalia; Maifoshie, Evie; Kelly, Douglas J.; McGovern, Ursula B.; Monteiro, Lara J.; Gomes, Ana R.; Nebreda, Angel R.; Campbell, David G.; Arthur, J. Simon C.; Lam, Eric W. -F.

In: Journal of Biological Chemistry, Vol. 287, No. 2, 06.01.2012, p. 1545-1555.

Research output: Contribution to journalArticle

Harvard

Ho, K-K, McGuire, VA, Koo, C-Y, Muir, KW, de Olano, N, Maifoshie, E, Kelly, DJ, McGovern, UB, Monteiro, LJ, Gomes, AR, Nebreda, AR, Campbell, DG, Arthur, JSC & Lam, EW-F 2012, 'Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin' Journal of Biological Chemistry, vol 287, no. 2, pp. 1545-1555.

APA

Ho, K-K., McGuire, V. A., Koo, C-Y., Muir, K. W., de Olano, N., Maifoshie, E., Kelly, D. J., McGovern, U. B., Monteiro, L. J., Gomes, A. R., Nebreda, A. R., Campbell, D. G., Arthur, J. S. C., & Lam, E. W. -F. (2012). Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin. Journal of Biological Chemistry, 287(2), 1545-1555doi: 10.1074/jbc.M111.284224

Vancouver

Ho K-K, McGuire VA, Koo C-Y, Muir KW, de Olano N, Maifoshie E et al. Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin. Journal of Biological Chemistry. 2012 Jan 6;287(2):1545-1555.

Author

Ho, Ka-Kei; McGuire, Victoria A.; Koo, Chuay-Yeng; Muir, Kyle W.; de Olano, Natalia; Maifoshie, Evie; Kelly, Douglas J.; McGovern, Ursula B.; Monteiro, Lara J.; Gomes, Ana R.; Nebreda, Angel R.; Campbell, David G.; Arthur, J. Simon C.; Lam, Eric W. -F. / Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin.

In: Journal of Biological Chemistry, Vol. 287, No. 2, 06.01.2012, p. 1545-1555.

Research output: Contribution to journalArticle

Bibtex - Download

@article{71369e05770c4fcf9f40ad77710a33d4,
title = "Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin",
author = "Ka-Kei Ho and McGuire, {Victoria A.} and Chuay-Yeng Koo and Muir, {Kyle W.} and {de Olano}, Natalia and Evie Maifoshie and Kelly, {Douglas J.} and McGovern, {Ursula B.} and Monteiro, {Lara J.} and Gomes, {Ana R.} and Nebreda, {Angel R.} and Campbell, {David G.} and Arthur, {J. Simon C.} and Lam, {Eric W. -F.}",
year = "2012",
volume = "287",
number = "2",
pages = "1545--1555",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin

A1 - Ho,Ka-Kei

A1 - McGuire,Victoria A.

A1 - Koo,Chuay-Yeng

A1 - Muir,Kyle W.

A1 - de Olano,Natalia

A1 - Maifoshie,Evie

A1 - Kelly,Douglas J.

A1 - McGovern,Ursula B.

A1 - Monteiro,Lara J.

A1 - Gomes,Ana R.

A1 - Nebreda,Angel R.

A1 - Campbell,David G.

A1 - Arthur,J. Simon C.

A1 - Lam,Eric W. -F.

AU - Ho,Ka-Kei

AU - McGuire,Victoria A.

AU - Koo,Chuay-Yeng

AU - Muir,Kyle W.

AU - de Olano,Natalia

AU - Maifoshie,Evie

AU - Kelly,Douglas J.

AU - McGovern,Ursula B.

AU - Monteiro,Lara J.

AU - Gomes,Ana R.

AU - Nebreda,Angel R.

AU - Campbell,David G.

AU - Arthur,J. Simon C.

AU - Lam,Eric W. -F.

PY - 2012/1/6

Y1 - 2012/1/6

N2 - <p>FOXO3a is a forkhead transcription factor that regulates a multitude of important cellular processes, including proliferation, apoptosis, differentiation, and metabolism. Doxorubicin treatment of MCF-7 breast carcinoma cells results in FOXO3a nuclear relocation and the induction of the stress-activated kinase p38 MAPK. Here, we studied the potential regulation of FOXO3a by p38 in response to doxorubicin. Co-immunoprecipitation studies in MCF-7 cells demonstrated a direct interaction between p38 and FOXO3a. We also showed that p38 can bind and phosphorylate a recombinant FOXO3a directly in vitro. HPLC-coupled phosphopeptide mapping and mass spectrometric analyses identified serine 7 as a major site for p38 phosphorylation. Using a phosphorylated Ser-7 FOXO3a antibody, we demonstrated that FOXO3a is phosphorylated on Ser-7 in response to doxorubicin. Immunofluorescence staining studies showed that upon doxorubicin treatment, the wild-type FOXO3a relocalized to the nucleus, whereas the phosphorylation-defective FOXO3a (Ala-7) mutant remained largely in the cytoplasm. Treatment with SB202190 also inhibits the doxorubicin-induced FOXO3a Ser-7 phosphorylation and nuclear accumulation in MCF-7 cells. In addition, doxorubicin caused the nuclear translocation of FOXO3a in wild-type but not p38-depleted mouse fibroblasts. Together, our results suggest that p38 phosphorylation of FOXO3a on Ser-7 is essential for its nuclear relocalization in response to doxorubicin.</p>

AB - <p>FOXO3a is a forkhead transcription factor that regulates a multitude of important cellular processes, including proliferation, apoptosis, differentiation, and metabolism. Doxorubicin treatment of MCF-7 breast carcinoma cells results in FOXO3a nuclear relocation and the induction of the stress-activated kinase p38 MAPK. Here, we studied the potential regulation of FOXO3a by p38 in response to doxorubicin. Co-immunoprecipitation studies in MCF-7 cells demonstrated a direct interaction between p38 and FOXO3a. We also showed that p38 can bind and phosphorylate a recombinant FOXO3a directly in vitro. HPLC-coupled phosphopeptide mapping and mass spectrometric analyses identified serine 7 as a major site for p38 phosphorylation. Using a phosphorylated Ser-7 FOXO3a antibody, we demonstrated that FOXO3a is phosphorylated on Ser-7 in response to doxorubicin. Immunofluorescence staining studies showed that upon doxorubicin treatment, the wild-type FOXO3a relocalized to the nucleus, whereas the phosphorylation-defective FOXO3a (Ala-7) mutant remained largely in the cytoplasm. Treatment with SB202190 also inhibits the doxorubicin-induced FOXO3a Ser-7 phosphorylation and nuclear accumulation in MCF-7 cells. In addition, doxorubicin caused the nuclear translocation of FOXO3a in wild-type but not p38-depleted mouse fibroblasts. Together, our results suggest that p38 phosphorylation of FOXO3a on Ser-7 is essential for its nuclear relocalization in response to doxorubicin.</p>

U2 - 10.1074/jbc.M111.284224

DO - 10.1074/jbc.M111.284224

M1 - Article

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 2

VL - 287

SP - 1545

EP - 1555

ER -

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