Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation

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Standard

Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. / Liu, Julio C.Y.; Ackermann, Leena; Hoffmann, Saskia; Gál, Zita; Hendriks, Ivo A.; Jain, Charu; Morlot, Louise; Tatham, Michael H.; McLelland, Gian-Luca; Hay, Ronald T.; Nielsen, Michael Lund; Brummelkamp, Thijn; Haahr, Peter; Mailand, Niels.

I: Nature Structural and Molecular Biology, 2024.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Liu, JCY, Ackermann, L, Hoffmann, S, Gál, Z, Hendriks, IA, Jain, C, Morlot, L, Tatham, MH, McLelland, G-L, Hay, RT, Nielsen, ML, Brummelkamp, T, Haahr, P & Mailand, N 2024, 'Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation', Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-024-01294-7

APA

Liu, J. C. Y., Ackermann, L., Hoffmann, S., Gál, Z., Hendriks, I. A., Jain, C., Morlot, L., Tatham, M. H., McLelland, G-L., Hay, R. T., Nielsen, M. L., Brummelkamp, T., Haahr, P., & Mailand, N. (2024). Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. Nature Structural and Molecular Biology. https://doi.org/10.1038/s41594-024-01294-7

Vancouver

Liu JCY, Ackermann L, Hoffmann S, Gál Z, Hendriks IA, Jain C o.a. Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. Nature Structural and Molecular Biology. 2024. https://doi.org/10.1038/s41594-024-01294-7

Author

Liu, Julio C.Y. ; Ackermann, Leena ; Hoffmann, Saskia ; Gál, Zita ; Hendriks, Ivo A. ; Jain, Charu ; Morlot, Louise ; Tatham, Michael H. ; McLelland, Gian-Luca ; Hay, Ronald T. ; Nielsen, Michael Lund ; Brummelkamp, Thijn ; Haahr, Peter ; Mailand, Niels. / Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. I: Nature Structural and Molecular Biology. 2024.

Bibtex

@article{526c5240e0b341409402d8f247821f35,
title = "Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation",
abstract = "Protein SUMOylation provides a principal driving force for cellular stress responses, including DNA–protein crosslink (DPC) repair and arsenic-induced PML body degradation. In this study, using genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL), combining ubiquitin ligase activity through its RING domain with poly-SUMO binding via SUMO-interacting motifs, analogous to the STUbL RNF4. Mechanistically, TOPORS is a SUMO1-selective STUbL that complements RNF4 in generating complex ubiquitin landscapes on SUMOylated targets, including DPCs and PML, stimulating efficient p97/VCP unfoldase recruitment and proteasomal degradation. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, involving defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Our findings establish TOPORS as a STUbL whose parallel action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO–ubiquitin crosstalk.",
author = "Liu, {Julio C.Y.} and Leena Ackermann and Saskia Hoffmann and Zita G{\'a}l and Hendriks, {Ivo A.} and Charu Jain and Louise Morlot and Tatham, {Michael H.} and Gian-Luca McLelland and Hay, {Ronald T.} and Nielsen, {Michael Lund} and Thijn Brummelkamp and Peter Haahr and Niels Mailand",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
doi = "10.1038/s41594-024-01294-7",
language = "English",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation

AU - Liu, Julio C.Y.

AU - Ackermann, Leena

AU - Hoffmann, Saskia

AU - Gál, Zita

AU - Hendriks, Ivo A.

AU - Jain, Charu

AU - Morlot, Louise

AU - Tatham, Michael H.

AU - McLelland, Gian-Luca

AU - Hay, Ronald T.

AU - Nielsen, Michael Lund

AU - Brummelkamp, Thijn

AU - Haahr, Peter

AU - Mailand, Niels

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - Protein SUMOylation provides a principal driving force for cellular stress responses, including DNA–protein crosslink (DPC) repair and arsenic-induced PML body degradation. In this study, using genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL), combining ubiquitin ligase activity through its RING domain with poly-SUMO binding via SUMO-interacting motifs, analogous to the STUbL RNF4. Mechanistically, TOPORS is a SUMO1-selective STUbL that complements RNF4 in generating complex ubiquitin landscapes on SUMOylated targets, including DPCs and PML, stimulating efficient p97/VCP unfoldase recruitment and proteasomal degradation. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, involving defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Our findings establish TOPORS as a STUbL whose parallel action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO–ubiquitin crosstalk.

AB - Protein SUMOylation provides a principal driving force for cellular stress responses, including DNA–protein crosslink (DPC) repair and arsenic-induced PML body degradation. In this study, using genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL), combining ubiquitin ligase activity through its RING domain with poly-SUMO binding via SUMO-interacting motifs, analogous to the STUbL RNF4. Mechanistically, TOPORS is a SUMO1-selective STUbL that complements RNF4 in generating complex ubiquitin landscapes on SUMOylated targets, including DPCs and PML, stimulating efficient p97/VCP unfoldase recruitment and proteasomal degradation. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, involving defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Our findings establish TOPORS as a STUbL whose parallel action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO–ubiquitin crosstalk.

U2 - 10.1038/s41594-024-01294-7

DO - 10.1038/s41594-024-01294-7

M3 - Journal article

C2 - 38649616

AN - SCOPUS:85191062272

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

ER -

ID: 394714723