AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. / Ghodke, Indrajeet; Remisova, Michaela; Furst, Audrey; Kilic, Sinan; Reina-San-Martin, Bernardo; Poetsch, Anna R.; Altmeyer, Matthias; Soutoglou, Evi.

In: Molecular Cell, Vol. 81, No. 12, 2021, p. 2596-2610.e7.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ghodke, I, Remisova, M, Furst, A, Kilic, S, Reina-San-Martin, B, Poetsch, AR, Altmeyer, M & Soutoglou, E 2021, 'AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation', Molecular Cell, vol. 81, no. 12, pp. 2596-2610.e7. https://doi.org/10.1016/j.molcel.2021.04.010

APA

Ghodke, I., Remisova, M., Furst, A., Kilic, S., Reina-San-Martin, B., Poetsch, A. R., Altmeyer, M., & Soutoglou, E. (2021). AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. Molecular Cell, 81(12), 2596-2610.e7. https://doi.org/10.1016/j.molcel.2021.04.010

Vancouver

Ghodke I, Remisova M, Furst A, Kilic S, Reina-San-Martin B, Poetsch AR et al. AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. Molecular Cell. 2021;81(12):2596-2610.e7. https://doi.org/10.1016/j.molcel.2021.04.010

Author

Ghodke, Indrajeet ; Remisova, Michaela ; Furst, Audrey ; Kilic, Sinan ; Reina-San-Martin, Bernardo ; Poetsch, Anna R. ; Altmeyer, Matthias ; Soutoglou, Evi. / AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. In: Molecular Cell. 2021 ; Vol. 81, No. 12. pp. 2596-2610.e7.

Bibtex

@article{ff1e2e9bbbda44ec87875dcc0f1e3a9c,
title = "AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation",
abstract = "p53-binding protein 1 (53BP1) regulates both the DNA damage response and p53 signaling. Although 53BP1's function is well established in DNA double-strand break repair, how its role in p53 signaling is modulated remains poorly understood. Here, we identify the scaffolding protein AHNAK as a G1 phase-enriched interactor of 53BP1. We demonstrate that AHNAK binds to the 53BP1 oligomerization domain and controls its multimerization potential. Loss of AHNAK results in hyper-accumulation of 53BP1 on chromatin and enhanced phase separation, culminating in an elevated p53 response, compromising cell survival in cancer cells but leading to senescence in non-transformed cells. Cancer transcriptome analyses indicate that AHNAK-53BP1 cooperation contributes to the suppression of p53 target gene networks in tumors and that loss of AHNAK sensitizes cells to combinatorial cancer treatments. These findings highlight AHNAK as a rheostat of 53BP1 function, which surveys cell proliferation by preventing an excessive p53 response.",
keywords = "DNA-DAMAGE, REPLICATION STRESS, TUMOR-SUPPRESSOR, PROTEIN, G1, ACTIVATION, REPAIR, PROLIFERATION, QUIESCENCE, PROGNOSIS",
author = "Indrajeet Ghodke and Michaela Remisova and Audrey Furst and Sinan Kilic and Bernardo Reina-San-Martin and Poetsch, {Anna R.} and Matthias Altmeyer and Evi Soutoglou",
year = "2021",
doi = "10.1016/j.molcel.2021.04.010",
language = "English",
volume = "81",
pages = "2596--2610.e7",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "12",

}

RIS

TY - JOUR

T1 - AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation

AU - Ghodke, Indrajeet

AU - Remisova, Michaela

AU - Furst, Audrey

AU - Kilic, Sinan

AU - Reina-San-Martin, Bernardo

AU - Poetsch, Anna R.

AU - Altmeyer, Matthias

AU - Soutoglou, Evi

PY - 2021

Y1 - 2021

N2 - p53-binding protein 1 (53BP1) regulates both the DNA damage response and p53 signaling. Although 53BP1's function is well established in DNA double-strand break repair, how its role in p53 signaling is modulated remains poorly understood. Here, we identify the scaffolding protein AHNAK as a G1 phase-enriched interactor of 53BP1. We demonstrate that AHNAK binds to the 53BP1 oligomerization domain and controls its multimerization potential. Loss of AHNAK results in hyper-accumulation of 53BP1 on chromatin and enhanced phase separation, culminating in an elevated p53 response, compromising cell survival in cancer cells but leading to senescence in non-transformed cells. Cancer transcriptome analyses indicate that AHNAK-53BP1 cooperation contributes to the suppression of p53 target gene networks in tumors and that loss of AHNAK sensitizes cells to combinatorial cancer treatments. These findings highlight AHNAK as a rheostat of 53BP1 function, which surveys cell proliferation by preventing an excessive p53 response.

AB - p53-binding protein 1 (53BP1) regulates both the DNA damage response and p53 signaling. Although 53BP1's function is well established in DNA double-strand break repair, how its role in p53 signaling is modulated remains poorly understood. Here, we identify the scaffolding protein AHNAK as a G1 phase-enriched interactor of 53BP1. We demonstrate that AHNAK binds to the 53BP1 oligomerization domain and controls its multimerization potential. Loss of AHNAK results in hyper-accumulation of 53BP1 on chromatin and enhanced phase separation, culminating in an elevated p53 response, compromising cell survival in cancer cells but leading to senescence in non-transformed cells. Cancer transcriptome analyses indicate that AHNAK-53BP1 cooperation contributes to the suppression of p53 target gene networks in tumors and that loss of AHNAK sensitizes cells to combinatorial cancer treatments. These findings highlight AHNAK as a rheostat of 53BP1 function, which surveys cell proliferation by preventing an excessive p53 response.

KW - DNA-DAMAGE

KW - REPLICATION STRESS

KW - TUMOR-SUPPRESSOR

KW - PROTEIN

KW - G1

KW - ACTIVATION

KW - REPAIR

KW - PROLIFERATION

KW - QUIESCENCE

KW - PROGNOSIS

U2 - 10.1016/j.molcel.2021.04.010

DO - 10.1016/j.molcel.2021.04.010

M3 - Journal article

C2 - 33961796

VL - 81

SP - 2596-2610.e7

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 12

ER -

ID: 275483627