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The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage

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The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage. / Nicol, S.M.; Bray, S.E.; Derek Black, H.; Lorimore, S.A.; Wright, E.G.; Lane, D.P.; Meek, D.W.; Coates, P.J.; Fuller-Pace, F.V. (Lead / Corresponding author).

In: Oncogene, Vol. 32, No. 29, 18.07.2013, p. 3461-3469.

Research output: Contribution to journalArticle

Harvard

Nicol, SM, Bray, SE, Derek Black, H, Lorimore, SA, Wright, EG, Lane, DP, Meek, DW, Coates, PJ & Fuller-Pace, FV 2013, 'The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage' Oncogene, vol 32, no. 29, pp. 3461-3469.

APA

Nicol, S. M., Bray, S. E., Derek Black, H., Lorimore, S. A., Wright, E. G., Lane, D. P., Meek, D. W., Coates, P. J., & Fuller-Pace, F. V. (2013). The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage. Oncogene, 32(29), 3461-3469doi: 10.1038/onc.2012.426

Vancouver

Nicol SM, Bray SE, Derek Black H, Lorimore SA, Wright EG, Lane DP et al. The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage. Oncogene. 2013 Jul 18;32(29):3461-3469.

Author

Nicol, S.M.; Bray, S.E.; Derek Black, H.; Lorimore, S.A.; Wright, E.G.; Lane, D.P.; Meek, D.W.; Coates, P.J.; Fuller-Pace, F.V. (Lead / Corresponding author) / The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage.

In: Oncogene, Vol. 32, No. 29, 18.07.2013, p. 3461-3469.

Research output: Contribution to journalArticle

Bibtex - Download

@article{7d00f73f3ce44893a53ab90e32f4690d,
title = "The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage",
author = "S.M. Nicol and S.E. Bray and {Derek Black}, H. and S.A. Lorimore and E.G. Wright and D.P. Lane and D.W. Meek and P.J. Coates and F.V. Fuller-Pace",
year = "2013",
volume = "32",
number = "29",
pages = "3461--3469",
journal = "Oncogene",
issn = "0950-9232",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage

A1 - Nicol,S.M.

A1 - Bray,S.E.

A1 - Derek Black,H.

A1 - Lorimore,S.A.

A1 - Wright,E.G.

A1 - Lane,D.P.

A1 - Meek,D.W.

A1 - Coates,P.J.

A1 - Fuller-Pace,F.V.

AU - Nicol,S.M.

AU - Bray,S.E.

AU - Derek Black,H.

AU - Lorimore,S.A.

AU - Wright,E.G.

AU - Lane,D.P.

AU - Meek,D.W.

AU - Coates,P.J.

AU - Fuller-Pace,F.V.

PY - 2013/7/18

Y1 - 2013/7/18

N2 - The RNA helicase p68 (DDX5) is an established co-activator of the p53 tumour suppressor that itself has a pivotal role in orchestrating the cellular response to DNA damage. Although several factors influence the biological outcome of p53 activation, the mechanisms governing the choice between cell-cycle arrest and apoptosis remain to be elucidated. In the present study, we show that, while p68 is critical for p53-mediated transactivation of the cell-cycle arrest gene p21 , it is dispensable for induction of several pro-apoptotic genes in response to DNA damage. Moreover, p68 depletion results in a striking inhibition of recruitment of p53 and RNA Pol II to the p21 promoter but not to the Bax or PUMA promoters, providing an explanation for the selective effect on p21 induction. Importantly, these findings are mirrored in a novel inducible p68 knockout mouse model in which p68 depletion results in a selective inhibition of p21 induction in several tissues. Moreover, in the bone marrow, p68 depletion results in an increased sensitivity to ?-irradiation, consistent with an increased level of apoptosis. These data highlight a novel function of p68 as a modulator of the decision between p53-mediated growth arrest and apoptosis in vitro and in vivo.Oncogene advance online publication, 17 September 2012; doi:10.1038/onc.2012.426.

AB - The RNA helicase p68 (DDX5) is an established co-activator of the p53 tumour suppressor that itself has a pivotal role in orchestrating the cellular response to DNA damage. Although several factors influence the biological outcome of p53 activation, the mechanisms governing the choice between cell-cycle arrest and apoptosis remain to be elucidated. In the present study, we show that, while p68 is critical for p53-mediated transactivation of the cell-cycle arrest gene p21 , it is dispensable for induction of several pro-apoptotic genes in response to DNA damage. Moreover, p68 depletion results in a striking inhibition of recruitment of p53 and RNA Pol II to the p21 promoter but not to the Bax or PUMA promoters, providing an explanation for the selective effect on p21 induction. Importantly, these findings are mirrored in a novel inducible p68 knockout mouse model in which p68 depletion results in a selective inhibition of p21 induction in several tissues. Moreover, in the bone marrow, p68 depletion results in an increased sensitivity to ?-irradiation, consistent with an increased level of apoptosis. These data highlight a novel function of p68 as a modulator of the decision between p53-mediated growth arrest and apoptosis in vitro and in vivo.Oncogene advance online publication, 17 September 2012; doi:10.1038/onc.2012.426.

U2 - 10.1038/onc.2012.426

DO - 10.1038/onc.2012.426

M1 - Article

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 29

VL - 32

SP - 3461

EP - 3469

ER -

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