Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

Ryosuke Shirasaki; Geoffrey M. Matthews; Sara Gandolfi; Ricardo de Matos Simoes; Dennis L. Buckley; Joseline Raja Vora; Quinlan L. Sievers; Johanna B. Brüggenthies; Olga Dashevsky; Haley Poarch; Huihui Tang; Megan A. Bariteau; Michal Sheffer; Yiguo Hu; Sondra L. Downey-Kopyscinski; Paul J. Hengeveld; Brian J. Glassner; Eugen Dhimolea; Christopher J. Ott; Tinghu Zhang; Nicholas P. Kwiatkowski; Jacob P. Laubach; Robert L. Schlossman; Paul G. Richardson; Aedin C. Culhane; Richard W.J. Groen; Eric S. Fischer; Francisca Vazquez; Aviad Tsherniak; William C. Hahn; Joan Levy; Daniel Auclair; Jonathan D. Licht; Jonathan J. Keats; Lawrence H. Boise; Benjamin L. Ebert; James E. Bradner; Nathanael S. Gray; Constantine S. Mitsiades

doi:10.1016/j.celrep.2020.108532

Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

Ryosuke Shirasaki, Geoffrey M. Matthews, Sara Gandolfi, Ricardo de Matos Simoes, Dennis L. Buckley, Joseline Raja Vora, Quinlan L. Sievers, Johanna B. Brüggenthies, Olga Dashevsky, Haley Poarch, Huihui Tang, Megan A. Bariteau, Michal Sheffer, Yiguo Hu, Sondra L. Downey-Kopyscinski, Paul J. Hengeveld, Brian J. Glassner, Eugen Dhimolea, Christopher J. Ott, Tinghu ZhangNicholas P. Kwiatkowski, Jacob P. Laubach, Robert L. Schlossman, Paul G. Richardson, Aedin C. Culhane, Richard W.J. Groen, Eric S. Fischer, Francisca Vazquez, Aviad Tsherniak, William C. Hahn, Joan Levy, Daniel Auclair, Jonathan D. Licht, Jonathan J. Keats, Lawrence H. Boise, Benjamin L. Ebert, James E. Bradner, Nathanael S. Gray, Constantine S. Mitsiades

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

Abstract

Genome-scale CRISPR gene editing studies by Shirasaki et al. reveal which genes confer myeloma cell resistance to PROTACs that leverage different E3 ligases to degrade various oncoproteins. The study provides a framework for sequential/alternating versus combined use of PROTACs, depending on which E3 ligase and oncoprotein they engage.

Original language	English
Article number	108532
Journal	Cell Reports
Volume	34
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2020.108532
Publication status	Published - 5 Jan 2021
Externally published	Yes

Keywords

CRBN
CRISPR
CRISPR activation
E3 ligase
PROTAC
VHL
heterobifunctional proteolysis-targeting chimeric compounds
myeloma
pharmacological degraders
resistance

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2020.108532

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Shirasaki, R., Matthews, G. M., Gandolfi, S., de Matos Simoes, R., Buckley, D. L., Raja Vora, J., Sievers, Q. L., Brüggenthies, J. B., Dashevsky, O., Poarch, H., Tang, H., Bariteau, M. A., Sheffer, M., Hu, Y., Downey-Kopyscinski, S. L., Hengeveld, P. J., Glassner, B. J., Dhimolea, E., Ott, C. J., ... Mitsiades, C. S. (2021). Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins. Cell Reports, 34(1), Article 108532. https://doi.org/10.1016/j.celrep.2020.108532

@article{a3666509e38c4ceb8f8bc529bdb7052f,

title = "Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins",

abstract = "Genome-scale CRISPR gene editing studies by Shirasaki et al. reveal which genes confer myeloma cell resistance to PROTACs that leverage different E3 ligases to degrade various oncoproteins. The study provides a framework for sequential/alternating versus combined use of PROTACs, depending on which E3 ligase and oncoprotein they engage.",

keywords = "CRBN, CRISPR, CRISPR activation, E3 ligase, PROTAC, VHL, heterobifunctional proteolysis-targeting chimeric compounds, myeloma, pharmacological degraders, resistance",

author = "Ryosuke Shirasaki and Matthews, \{Geoffrey M.\} and Sara Gandolfi and \{de Matos Simoes\}, Ricardo and Buckley, \{Dennis L.\} and \{Raja Vora\}, Joseline and Sievers, \{Quinlan L.\} and Br{\"u}ggenthies, \{Johanna B.\} and Olga Dashevsky and Haley Poarch and Huihui Tang and Bariteau, \{Megan A.\} and Michal Sheffer and Yiguo Hu and Downey-Kopyscinski, \{Sondra L.\} and Hengeveld, \{Paul J.\} and Glassner, \{Brian J.\} and Eugen Dhimolea and Ott, \{Christopher J.\} and Tinghu Zhang and Kwiatkowski, \{Nicholas P.\} and Laubach, \{Jacob P.\} and Schlossman, \{Robert L.\} and Richardson, \{Paul G.\} and Culhane, \{Aedin C.\} and Groen, \{Richard W.J.\} and Fischer, \{Eric S.\} and Francisca Vazquez and Aviad Tsherniak and Hahn, \{William C.\} and Joan Levy and Daniel Auclair and Licht, \{Jonathan D.\} and Keats, \{Jonathan J.\} and Boise, \{Lawrence H.\} and Ebert, \{Benjamin L.\} and Bradner, \{James E.\} and Gray, \{Nathanael S.\} and Mitsiades, \{Constantine S.\}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = jan,

day = "5",

doi = "10.1016/j.celrep.2020.108532",

language = "English",

volume = "34",

journal = "Cell Reports",

issn = "2211-1247",

number = "1",

}

Shirasaki, R, Matthews, GM, Gandolfi, S, de Matos Simoes, R, Buckley, DL, Raja Vora, J, Sievers, QL, Brüggenthies, JB, Dashevsky, O, Poarch, H, Tang, H, Bariteau, MA, Sheffer, M, Hu, Y, Downey-Kopyscinski, SL, Hengeveld, PJ, Glassner, BJ, Dhimolea, E, Ott, CJ, Zhang, T, Kwiatkowski, NP, Laubach, JP, Schlossman, RL, Richardson, PG, Culhane, AC, Groen, RWJ, Fischer, ES, Vazquez, F, Tsherniak, A, Hahn, WC, Levy, J, Auclair, D, Licht, JD, Keats, JJ, Boise, LH, Ebert, BL, Bradner, JE, Gray, NS & Mitsiades, CS 2021, 'Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins', Cell Reports, vol. 34, no. 1, 108532. https://doi.org/10.1016/j.celrep.2020.108532

TY - JOUR

T1 - Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

AU - Shirasaki, Ryosuke

AU - Matthews, Geoffrey M.

AU - Gandolfi, Sara

AU - de Matos Simoes, Ricardo

AU - Buckley, Dennis L.

AU - Raja Vora, Joseline

AU - Sievers, Quinlan L.

AU - Brüggenthies, Johanna B.

AU - Dashevsky, Olga

AU - Poarch, Haley

AU - Tang, Huihui

AU - Bariteau, Megan A.

AU - Sheffer, Michal

AU - Hu, Yiguo

AU - Downey-Kopyscinski, Sondra L.

AU - Hengeveld, Paul J.

AU - Glassner, Brian J.

AU - Dhimolea, Eugen

AU - Ott, Christopher J.

AU - Zhang, Tinghu

AU - Kwiatkowski, Nicholas P.

AU - Laubach, Jacob P.

AU - Schlossman, Robert L.

AU - Richardson, Paul G.

AU - Culhane, Aedin C.

AU - Groen, Richard W.J.

AU - Fischer, Eric S.

AU - Vazquez, Francisca

AU - Tsherniak, Aviad

AU - Hahn, William C.

AU - Levy, Joan

AU - Auclair, Daniel

AU - Licht, Jonathan D.

AU - Keats, Jonathan J.

AU - Boise, Lawrence H.

AU - Ebert, Benjamin L.

AU - Bradner, James E.

AU - Gray, Nathanael S.

AU - Mitsiades, Constantine S.

PY - 2021/1/5

Y1 - 2021/1/5

N2 - Genome-scale CRISPR gene editing studies by Shirasaki et al. reveal which genes confer myeloma cell resistance to PROTACs that leverage different E3 ligases to degrade various oncoproteins. The study provides a framework for sequential/alternating versus combined use of PROTACs, depending on which E3 ligase and oncoprotein they engage.

AB - Genome-scale CRISPR gene editing studies by Shirasaki et al. reveal which genes confer myeloma cell resistance to PROTACs that leverage different E3 ligases to degrade various oncoproteins. The study provides a framework for sequential/alternating versus combined use of PROTACs, depending on which E3 ligase and oncoprotein they engage.

KW - CRBN

KW - CRISPR

KW - CRISPR activation

KW - E3 ligase

KW - PROTAC

KW - VHL

KW - heterobifunctional proteolysis-targeting chimeric compounds

KW - myeloma

KW - pharmacological degraders

KW - resistance

UR - https://www.scopus.com/pages/publications/85099249564

U2 - 10.1016/j.celrep.2020.108532

DO - 10.1016/j.celrep.2020.108532

M3 - Article

C2 - 33406420

AN - SCOPUS:85099249564

SN - 2211-1247

VL - 34

JO - Cell Reports

JF - Cell Reports

IS - 1

M1 - 108532

ER -

Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

Abstract

Keywords

UN SDGs

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