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PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis

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PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis. / Li, Caiyun G; Mahon, Cathal; Sweeney, Nathaly M; Verschueren, Erik; Kantamani, Vivek; Li, Dan; Hennigs, Jan K; Marciano, David P; Diebold, Isabel; Abu-Halawa, Ossama; Elliott, Matthew; Sa, Silin; Guo, Feng; Wang, Lingli; Cao, Aiqin; Guignabert, Christophe; Sollier, Julie; Nickel, Nils P; Kaschwich, Mark; Cimprich, Karlene A; Rabinovitch, Marlene.

in: CELL REP, Jahrgang 26, Nr. 5, 29.01.2019, S. 1333-1343.e7.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Li, CG, Mahon, C, Sweeney, NM, Verschueren, E, Kantamani, V, Li, D, Hennigs, JK, Marciano, DP, Diebold, I, Abu-Halawa, O, Elliott, M, Sa, S, Guo, F, Wang, L, Cao, A, Guignabert, C, Sollier, J, Nickel, NP, Kaschwich, M, Cimprich, KA & Rabinovitch, M 2019, 'PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis', CELL REP, Jg. 26, Nr. 5, S. 1333-1343.e7. https://doi.org/10.1016/j.celrep.2019.01.013

APA

Li, C. G., Mahon, C., Sweeney, N. M., Verschueren, E., Kantamani, V., Li, D., Hennigs, J. K., Marciano, D. P., Diebold, I., Abu-Halawa, O., Elliott, M., Sa, S., Guo, F., Wang, L., Cao, A., Guignabert, C., Sollier, J., Nickel, N. P., Kaschwich, M., ... Rabinovitch, M. (2019). PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis. CELL REP, 26(5), 1333-1343.e7. https://doi.org/10.1016/j.celrep.2019.01.013

Vancouver

Li CG, Mahon C, Sweeney NM, Verschueren E, Kantamani V, Li D et al. PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis. CELL REP. 2019 Jan 29;26(5):1333-1343.e7. https://doi.org/10.1016/j.celrep.2019.01.013

Bibtex

@article{191fbcc6fe3c49d6a8a8996c59e799b4,
title = "PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis",
abstract = "Using proteomic approaches, we uncovered a DNA damage response (DDR) function for peroxisome proliferator activated receptor γ (PPARγ) through its interaction with the DNA damage sensor MRE11-RAD50-NBS1 (MRN) and the E3 ubiquitin ligase UBR5. We show that PPARγ promotes ATM signaling and is essential for UBR5 activity targeting ATM interactor (ATMIN). PPARγ depletion increases ATMIN protein independent of transcription and suppresses DDR-induced ATM signaling. Blocking ATMIN in this context restores ATM activation and DNA repair. We illustrate the physiological relevance of PPARγ DDR functions by using pulmonary arterial hypertension (PAH) as a model that has impaired PPARγ signaling related to endothelial cell (EC) dysfunction and unresolved DNA damage. In pulmonary arterial ECs (PAECs) from PAH patients, we observed disrupted PPARγ-UBR5 interaction, heightened ATMIN expression, and DNA lesions. Blocking ATMIN in PAH PAEC restores ATM activation. Thus, impaired PPARγ DDR functions may explain the genomic instability and loss of endothelial homeostasis in PAH.",
keywords = "Journal Article",
author = "Li, {Caiyun G} and Cathal Mahon and Sweeney, {Nathaly M} and Erik Verschueren and Vivek Kantamani and Dan Li and Hennigs, {Jan K} and Marciano, {David P} and Isabel Diebold and Ossama Abu-Halawa and Matthew Elliott and Silin Sa and Feng Guo and Lingli Wang and Aiqin Cao and Christophe Guignabert and Julie Sollier and Nickel, {Nils P} and Mark Kaschwich and Cimprich, {Karlene A} and Marlene Rabinovitch",
note = "Copyright {\textcopyright} 2019 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = jan,
day = "29",
doi = "10.1016/j.celrep.2019.01.013",
language = "English",
volume = "26",
pages = "1333--1343.e7",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis

AU - Li, Caiyun G

AU - Mahon, Cathal

AU - Sweeney, Nathaly M

AU - Verschueren, Erik

AU - Kantamani, Vivek

AU - Li, Dan

AU - Hennigs, Jan K

AU - Marciano, David P

AU - Diebold, Isabel

AU - Abu-Halawa, Ossama

AU - Elliott, Matthew

AU - Sa, Silin

AU - Guo, Feng

AU - Wang, Lingli

AU - Cao, Aiqin

AU - Guignabert, Christophe

AU - Sollier, Julie

AU - Nickel, Nils P

AU - Kaschwich, Mark

AU - Cimprich, Karlene A

AU - Rabinovitch, Marlene

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2019/1/29

Y1 - 2019/1/29

N2 - Using proteomic approaches, we uncovered a DNA damage response (DDR) function for peroxisome proliferator activated receptor γ (PPARγ) through its interaction with the DNA damage sensor MRE11-RAD50-NBS1 (MRN) and the E3 ubiquitin ligase UBR5. We show that PPARγ promotes ATM signaling and is essential for UBR5 activity targeting ATM interactor (ATMIN). PPARγ depletion increases ATMIN protein independent of transcription and suppresses DDR-induced ATM signaling. Blocking ATMIN in this context restores ATM activation and DNA repair. We illustrate the physiological relevance of PPARγ DDR functions by using pulmonary arterial hypertension (PAH) as a model that has impaired PPARγ signaling related to endothelial cell (EC) dysfunction and unresolved DNA damage. In pulmonary arterial ECs (PAECs) from PAH patients, we observed disrupted PPARγ-UBR5 interaction, heightened ATMIN expression, and DNA lesions. Blocking ATMIN in PAH PAEC restores ATM activation. Thus, impaired PPARγ DDR functions may explain the genomic instability and loss of endothelial homeostasis in PAH.

AB - Using proteomic approaches, we uncovered a DNA damage response (DDR) function for peroxisome proliferator activated receptor γ (PPARγ) through its interaction with the DNA damage sensor MRE11-RAD50-NBS1 (MRN) and the E3 ubiquitin ligase UBR5. We show that PPARγ promotes ATM signaling and is essential for UBR5 activity targeting ATM interactor (ATMIN). PPARγ depletion increases ATMIN protein independent of transcription and suppresses DDR-induced ATM signaling. Blocking ATMIN in this context restores ATM activation and DNA repair. We illustrate the physiological relevance of PPARγ DDR functions by using pulmonary arterial hypertension (PAH) as a model that has impaired PPARγ signaling related to endothelial cell (EC) dysfunction and unresolved DNA damage. In pulmonary arterial ECs (PAECs) from PAH patients, we observed disrupted PPARγ-UBR5 interaction, heightened ATMIN expression, and DNA lesions. Blocking ATMIN in PAH PAEC restores ATM activation. Thus, impaired PPARγ DDR functions may explain the genomic instability and loss of endothelial homeostasis in PAH.

KW - Journal Article

U2 - 10.1016/j.celrep.2019.01.013

DO - 10.1016/j.celrep.2019.01.013

M3 - SCORING: Journal article

C2 - 30699358

VL - 26

SP - 1333-1343.e7

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 5

ER -