Home > Research > Publications & Outputs > ARF triggers senescence in Brca2-deficient cell...

Research

Links

Text available via DOI:

View graph of relations

ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets. / Carlos, A.R.; Escandell, J.M.; Kotsantis, P. et al.
In: Nature Communications, Vol. 4, 2697, 28.10.2013.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Carlos, AR, Escandell, JM, Kotsantis, P, Suwaki, N, Bouwman, P, Badie, S, Folio, C, Benitez, J, Gomez-Lopez, G, Pisano, DG, Jonkers, J & Tarsounas, M 2013, 'ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets', Nature Communications, vol. 4, 2697. https://doi.org/10.1038/ncomms3697

APA

Carlos, A. R., Escandell, J. M., Kotsantis, P., Suwaki, N., Bouwman, P., Badie, S., Folio, C., Benitez, J., Gomez-Lopez, G., Pisano, D. G., Jonkers, J., & Tarsounas, M. (2013). ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets. Nature Communications, 4, Article 2697. https://doi.org/10.1038/ncomms3697

Vancouver

Carlos AR, Escandell JM, Kotsantis P, Suwaki N, Bouwman P, Badie S et al. ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets. Nature Communications. 2013 Oct 28;4:2697. doi: 10.1038/ncomms3697

Author

Carlos, A.R. ; Escandell, J.M. ; Kotsantis, P. et al. / ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets. In: Nature Communications. 2013 ; Vol. 4.

Bibtex

@article{64ba1ff941424eb28aa54080211fec60,
title = "ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets",
abstract = "ARF is a tumour suppressor activated by oncogenic stress, which stabilizes p53. Although p53 is a key component of the response to DNA damage, a similar function for ARF has not been ascribed. Here we show that primary mouse and human cells lacking the tumour suppressor BRCA2 accumulate DNA damage, which triggers checkpoint signalling and ARF activation. Furthermore, senescence induced by Brca2 deletion in primary mouse and human cells is reversed by the loss of ARF, a phenotype recapitulated in cells lacking RAD51. Surprisingly, ARF is not necessary for p53 accumulation per se but for altering the spectrum of genes activated by this transcription factor. Specifically, ARF enables p53 transcription of Dusp4 and Dusp7, which encode a pair of phosphatases known to inactivate the MAP kinases ERK1/2. Our results ascribe a previously unanticipated function to the ARF tumour suppressor in genome integrity, controlled by replicative stress and ATM/ATR-dependent checkpoint responses.",
author = "A.R. Carlos and J.M. Escandell and P. Kotsantis and N. Suwaki and P. Bouwman and S. Badie and C. Folio and J. Benitez and G. Gomez-Lopez and D.G. Pisano and J. Jonkers and M. Tarsounas",
year = "2013",
month = oct,
day = "28",
doi = "10.1038/ncomms3697",
language = "English",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets

AU - Carlos, A.R.

AU - Escandell, J.M.

AU - Kotsantis, P.

AU - Suwaki, N.

AU - Bouwman, P.

AU - Badie, S.

AU - Folio, C.

AU - Benitez, J.

AU - Gomez-Lopez, G.

AU - Pisano, D.G.

AU - Jonkers, J.

AU - Tarsounas, M.

PY - 2013/10/28

Y1 - 2013/10/28

N2 - ARF is a tumour suppressor activated by oncogenic stress, which stabilizes p53. Although p53 is a key component of the response to DNA damage, a similar function for ARF has not been ascribed. Here we show that primary mouse and human cells lacking the tumour suppressor BRCA2 accumulate DNA damage, which triggers checkpoint signalling and ARF activation. Furthermore, senescence induced by Brca2 deletion in primary mouse and human cells is reversed by the loss of ARF, a phenotype recapitulated in cells lacking RAD51. Surprisingly, ARF is not necessary for p53 accumulation per se but for altering the spectrum of genes activated by this transcription factor. Specifically, ARF enables p53 transcription of Dusp4 and Dusp7, which encode a pair of phosphatases known to inactivate the MAP kinases ERK1/2. Our results ascribe a previously unanticipated function to the ARF tumour suppressor in genome integrity, controlled by replicative stress and ATM/ATR-dependent checkpoint responses.

AB - ARF is a tumour suppressor activated by oncogenic stress, which stabilizes p53. Although p53 is a key component of the response to DNA damage, a similar function for ARF has not been ascribed. Here we show that primary mouse and human cells lacking the tumour suppressor BRCA2 accumulate DNA damage, which triggers checkpoint signalling and ARF activation. Furthermore, senescence induced by Brca2 deletion in primary mouse and human cells is reversed by the loss of ARF, a phenotype recapitulated in cells lacking RAD51. Surprisingly, ARF is not necessary for p53 accumulation per se but for altering the spectrum of genes activated by this transcription factor. Specifically, ARF enables p53 transcription of Dusp4 and Dusp7, which encode a pair of phosphatases known to inactivate the MAP kinases ERK1/2. Our results ascribe a previously unanticipated function to the ARF tumour suppressor in genome integrity, controlled by replicative stress and ATM/ATR-dependent checkpoint responses.

U2 - 10.1038/ncomms3697

DO - 10.1038/ncomms3697

M3 - Journal article

VL - 4

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 2697

ER -