Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1

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

Standard

Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1. / Colding-Christensen, Camilla S; Kakulidis, Ellen S; Arroyo-Gomez, Javier; Hendriks, Ivo A; Arkinson, Connor; Fábián, Zita; Gambus, Agnieszka; Mailand, Niels; Duxin, Julien P; Nielsen, Michael L.

In: Nature Communications, Vol. 14, 8293, 2023.

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

Harvard

Colding-Christensen, CS, Kakulidis, ES, Arroyo-Gomez, J, Hendriks, IA, Arkinson, C, Fábián, Z, Gambus, A, Mailand, N, Duxin, JP & Nielsen, ML 2023, 'Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1', Nature Communications, vol. 14, 8293. https://doi.org/10.1038/s41467-023-43873-0

APA

Colding-Christensen, C. S., Kakulidis, E. S., Arroyo-Gomez, J., Hendriks, I. A., Arkinson, C., Fábián, Z., Gambus, A., Mailand, N., Duxin, J. P., & Nielsen, M. L. (2023). Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1. Nature Communications, 14, [8293]. https://doi.org/10.1038/s41467-023-43873-0

Vancouver

Colding-Christensen CS, Kakulidis ES, Arroyo-Gomez J, Hendriks IA, Arkinson C, Fábián Z et al. Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1. Nature Communications. 2023;14. 8293. https://doi.org/10.1038/s41467-023-43873-0

Author

Colding-Christensen, Camilla S ; Kakulidis, Ellen S ; Arroyo-Gomez, Javier ; Hendriks, Ivo A ; Arkinson, Connor ; Fábián, Zita ; Gambus, Agnieszka ; Mailand, Niels ; Duxin, Julien P ; Nielsen, Michael L. / Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1. In: Nature Communications. 2023 ; Vol. 14.

Bibtex

@article{4677abf93b044c88b721742037f2a806,
title = "Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1",
abstract = "Ubiquitin widely modifies proteins, thereby regulating most cellular functions. The complexity of ubiquitin signalling necessitates unbiased methods enabling global detection of dynamic protein ubiquitylation. Here, we describe UBIMAX (UBiquitin target Identification by Mass spectrometry in Xenopus egg extracts), which enriches ubiquitin-conjugated proteins and quantifies regulation of protein ubiquitylation under precise and adaptable conditions. We benchmark UBIMAX by investigating DNA double-strand break-responsive ubiquitylation events, identifying previously known targets and revealing the actin-organizing protein Dbn1 as a major target of DNA damage-induced ubiquitylation. We find that Dbn1 is targeted for proteasomal degradation by the SCFβ-Trcp1 ubiquitin ligase, in a conserved mechanism driven by ATM-mediated phosphorylation of a previously uncharacterized β-Trcp1 degron containing an SQ motif. We further show that this degron is sufficient to induce DNA damage-dependent protein degradation of a model substrate. Collectively, we demonstrate UBIMAX's ability to identify targets of stimulus-regulated ubiquitylation and reveal an SCFβ-Trcp1-mediated ubiquitylation mechanism controlled directly by the apical DNA damage response kinases.",
keywords = "Ubiquitin/metabolism, Actins/metabolism, Ubiquitination, Signal Transduction, DNA Damage",
author = "Colding-Christensen, {Camilla S} and Kakulidis, {Ellen S} and Javier Arroyo-Gomez and Hendriks, {Ivo A} and Connor Arkinson and Zita F{\'a}bi{\'a}n and Agnieszka Gambus and Niels Mailand and Duxin, {Julien P} and Nielsen, {Michael L}",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
doi = "10.1038/s41467-023-43873-0",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1

AU - Colding-Christensen, Camilla S

AU - Kakulidis, Ellen S

AU - Arroyo-Gomez, Javier

AU - Hendriks, Ivo A

AU - Arkinson, Connor

AU - Fábián, Zita

AU - Gambus, Agnieszka

AU - Mailand, Niels

AU - Duxin, Julien P

AU - Nielsen, Michael L

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - Ubiquitin widely modifies proteins, thereby regulating most cellular functions. The complexity of ubiquitin signalling necessitates unbiased methods enabling global detection of dynamic protein ubiquitylation. Here, we describe UBIMAX (UBiquitin target Identification by Mass spectrometry in Xenopus egg extracts), which enriches ubiquitin-conjugated proteins and quantifies regulation of protein ubiquitylation under precise and adaptable conditions. We benchmark UBIMAX by investigating DNA double-strand break-responsive ubiquitylation events, identifying previously known targets and revealing the actin-organizing protein Dbn1 as a major target of DNA damage-induced ubiquitylation. We find that Dbn1 is targeted for proteasomal degradation by the SCFβ-Trcp1 ubiquitin ligase, in a conserved mechanism driven by ATM-mediated phosphorylation of a previously uncharacterized β-Trcp1 degron containing an SQ motif. We further show that this degron is sufficient to induce DNA damage-dependent protein degradation of a model substrate. Collectively, we demonstrate UBIMAX's ability to identify targets of stimulus-regulated ubiquitylation and reveal an SCFβ-Trcp1-mediated ubiquitylation mechanism controlled directly by the apical DNA damage response kinases.

AB - Ubiquitin widely modifies proteins, thereby regulating most cellular functions. The complexity of ubiquitin signalling necessitates unbiased methods enabling global detection of dynamic protein ubiquitylation. Here, we describe UBIMAX (UBiquitin target Identification by Mass spectrometry in Xenopus egg extracts), which enriches ubiquitin-conjugated proteins and quantifies regulation of protein ubiquitylation under precise and adaptable conditions. We benchmark UBIMAX by investigating DNA double-strand break-responsive ubiquitylation events, identifying previously known targets and revealing the actin-organizing protein Dbn1 as a major target of DNA damage-induced ubiquitylation. We find that Dbn1 is targeted for proteasomal degradation by the SCFβ-Trcp1 ubiquitin ligase, in a conserved mechanism driven by ATM-mediated phosphorylation of a previously uncharacterized β-Trcp1 degron containing an SQ motif. We further show that this degron is sufficient to induce DNA damage-dependent protein degradation of a model substrate. Collectively, we demonstrate UBIMAX's ability to identify targets of stimulus-regulated ubiquitylation and reveal an SCFβ-Trcp1-mediated ubiquitylation mechanism controlled directly by the apical DNA damage response kinases.

KW - Ubiquitin/metabolism

KW - Actins/metabolism

KW - Ubiquitination

KW - Signal Transduction

KW - DNA Damage

U2 - 10.1038/s41467-023-43873-0

DO - 10.1038/s41467-023-43873-0

M3 - Journal article

C2 - 38097601

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8293

ER -

ID: 378868083