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E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. / Burdova, Kamila; Yang, Hongbin; Faedda, Roberta et al.

In: EMBO Journal, Vol. 38, No. 20, e101443, 15.10.2019.

Research output: Contribution to journal › Article › peer-review

Harvard

Burdova, K, Yang, H, Faedda, R, Hume, S, Chauhan, J, Ebner, D, Kessler, BM, Vendrell, I, Drewry, DH, Wells, CI, Hatch, SB, Dianov, GL, Buffa, FM & D'Angiolella, V 2019, 'E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition', EMBO Journal, vol. 38, no. 20, e101443. https://doi.org/10.15252/embj.2018101443

APA

Burdova, K., Yang, H., Faedda, R., Hume, S., Chauhan, J., Ebner, D., Kessler, B. M., Vendrell, I., Drewry, D. H., Wells, C. I., Hatch, S. B., Dianov, G. L., Buffa, F. M., & D'Angiolella, V. (2019). E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. EMBO Journal, 38(20), [e101443]. https://doi.org/10.15252/embj.2018101443

Vancouver

Burdova K, Yang H, Faedda R, Hume S, Chauhan J, Ebner D et al. E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. EMBO Journal. 2019 Oct 15;38(20):e101443. doi: 10.15252/embj.2018101443

Author

Burdova, Kamila ; Yang, Hongbin ; Faedda, Roberta et al. / E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. In: EMBO Journal. 2019 ; Vol. 38, No. 20.

BibTeX

@article{f9d43cfcf501470bb7df90417147b0d9,
title = "E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition",
abstract = "Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors.",
keywords = "cell cycle, checkpoints, Chk1, cyclin F, F-box proteins, BETA-TRCP, MEDIATED DEGRADATION, KINASE INHIBITOR, CDC25A, DNA-REPLICATION, POTENT, TUMOR-SUPPRESSOR, CHECKPOINT, STRESS, ATR",
author = "Kamila Burdova and Hongbin Yang and Roberta Faedda and Samuel Hume and Jagat Chauhan and Daniel Ebner and Kessler, {Benedikt M.} and Iolanda Vendrell and Drewry, {David H.} and Wells, {Carrow I.} and Hatch, {Stephanie B.} and Dianov, {Grigory L.} and Buffa, {Francesca M.} and Vincenzo D'Angiolella",
note = "Publisher Copyright: {\textcopyright} 2019 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2019",
month = oct,
day = "15",
doi = "10.15252/embj.2018101443",
language = "English",
volume = "38",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "20",

}

RIS

TY - JOUR

T1 - E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition

AU - Burdova, Kamila

AU - Yang, Hongbin

AU - Faedda, Roberta

AU - Hume, Samuel

AU - Chauhan, Jagat

AU - Ebner, Daniel

AU - Kessler, Benedikt M.

AU - Vendrell, Iolanda

AU - Drewry, David H.

AU - Wells, Carrow I.

AU - Hatch, Stephanie B.

AU - Dianov, Grigory L.

AU - Buffa, Francesca M.

AU - D'Angiolella, Vincenzo

N1 - Publisher Copyright: © 2019 The Authors. Published under the terms of the CC BY 4.0 license

PY - 2019/10/15

Y1 - 2019/10/15

N2 - Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors.

AB - Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors.

KW - cell cycle

KW - checkpoints

KW - Chk1

KW - cyclin F

KW - F-box proteins

KW - BETA-TRCP

KW - MEDIATED DEGRADATION

KW - KINASE INHIBITOR

KW - CDC25A

KW - DNA-REPLICATION

KW - POTENT

KW - TUMOR-SUPPRESSOR

KW - CHECKPOINT

KW - STRESS

KW - ATR

UR - http://www.scopus.com/inward/record.url?scp=85070839576&partnerID=8YFLogxK

U2 - 10.15252/embj.2018101443

DO - 10.15252/embj.2018101443

M3 - Article

C2 - 31424118

AN - SCOPUS:85070839576

VL - 38

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 20

M1 - e101443

ER -

ID: 21258091