Results 1 to 10 of about 3,357,183 (133)

Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death [PDF]

Nature Communications, 2019
PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG ...
Jerry H. Houl, Zu Ye, Chris A. Brosey, Lakshitha P. F. Balapiti-Modarage, Sarita Namjoshi, Albino Bacolla, Daniel Laverty, Brian L. Walker, Yasin Pourfarjam, Leslie S. Warden, Naga Babu Chinnam, Davide Moiani, Roderick A. Stegeman, Mei-Kuang Chen, Mien-Chie Hung, Zachary D. Nagel, Tom Ellenberger, In-Kwon Kim, Darin E. Jones, Zamal Ahmed, John A. Tainer   +20 more
doaj   +4 more sources

Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP‐ribose) glycohydrolase inhibitor [PDF]

FEBS Open Bio
Poly(ADP‐ribose) glycohydrolase (PARG) is a key enzyme involved in poly(ADP‐ribose) (PAR) degradation and is considered a potential anticancer target. We previously investigated resistance mechanisms to the PARG inhibitor PDD00017273 in human colorectal ...
Kaede Tsuda, Yoko Ogino, Akira Sato
doaj   +4 more sources

Loss‐of‐function genetic screen unveils synergistic efficacy of PARG inhibition with combined 5‐fluorouracil and irinotecan treatment in colorectal cancer [PDF]

Clinical and Translational Medicine
Background Colorectal cancer (CRC) remains a major global health concern, partly due to resistance to therapy and the lack of new effective treatments for advanced disease.
Cristina Queralt, Cristina Moreta‐Moraleda, Marta Costa, Ferran Grau‐Leal, Jeannine Diesch, Carla Vendrell‐Ayats, Eva Musulén, Roni H G Wright, Cristina Bugés, José Luis Manzano, Sara Cabrero‐de las Heras, Johannes Zuber, Marcus Buschbeck, Sonia‐V Forcales, Eva Martínez‐Balibrea   +14 more
doaj   +4 more sources

PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer [PDF]

Proceedings of the National Academy of Sciences of the United States of America
Significance As Poly (ADP-ribose) glycohydrolase (PARG) inhibitors are now in clinical trials, we evaluated the mechanism of replication defects resulting in tumor cell killing from PARG inhibition.
Alan D'Andrea, , Geoffrey Shapiro
exaly   +3 more sources

Synergistic Cellular Toxicity from Inhibition of Poly(ADP-ribose) Glycohydrolase (PARG) and Ubiquitin-Specific Protease 1 (USP1) [PDF]

Toxics
Ubiquitin-specific protease 1 (USP1) is an emerging target for poly(ADP-ribose) polymerase 1 (PARP1) inhibitor-resistant and BRCA1/BRCA2 mutant tumors.
Stefan M. Leonard, Charlotte R. Pearson, Wynand P. Roos, Robert W. Sobol   +3 more
doaj   +3 more sources

Intrinsic PARG inhibitor sensitivity is mimicked by TIMELESS haploinsufficiency and rescued by nucleoside supplementation. [PDF]

NAR Cancer
A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of TIMELESS,
Coulson-Gilmer C, Littler S, Barnes BM, Brady RM, Anagho HA, Pillay N, Dey M, Macmorland W, Bronder D, Nelson L, Tighe A, Lin WH, Morgan RD, Unwin RD, Nielsen ML, McGrail JC, Taylor SS.   +16 more
europepmc   +2 more sources

Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis. [PDF]

NAR Cancer
Poly(ADP-ribose) polymerases 1 and 2 (PARP1/PARP2), and poly(ADP-ribose) glycohydrolase (PARG), modulate the level of poly(ADP-ribose) (PAR), a post-translational protein modification, in response to DNA damage or replication stress.
Ibrahim M, Roos WP, Schwartz JC, Khan MM, Al-Rahahleh RQ, Beers LA, Pearson CR, Langham KT, Boyang L, Clark J, Hayat F, Fang Q, Koczor CA, Migaud ME, Sobol RW.   +14 more
europepmc   +2 more sources

Elevated TRIM25 Impairs Poly (ADP-ribose) Metabolism via PARG Degradation and Mediates Compression-Induced Intervertebral Disc Degeneration. [PDF]

Adv Sci (Weinh)
TRIM25 acts as a multifunctional hub driving intervertebral disc degeneration under mechanical stress. Mechanical compression significantly upregulates TRIM25 expression, establishing it as a key E3 ubiquitin ligase platform. TRIM25 targets PARG and Ku80 via distinct molecular interfaces, triggering their ubiquitination and degradation.
Cheng Z, Gao H, Wu W, Shi P, Chen X, Yu Z, Wu W, Zhao K, Yang C, Zhang Y.   +9 more
europepmc   +2 more sources

PARG inhibition suppresses breast cancer progression and potentiates immunoresponse through MTDH degradation mediated by E3 ligase ITCH-dependent ubiquitination [PDF]

npj Breast Cancer
PARG plays an important role in cancer progression and immunoresponse, but its role in breast cancer is not yet fully elucidated. The advanced breast cancer is still a persistent challenge in clinical oncology.
Junnai Wang, Yanhua Dong, Weiwei Lun, Manman Nai, Yajing Shi, Jianfang Geng, Wenhui Cai, Jiaxi Liu, Hongyu Li, Lei Li   +9 more
doaj   +2 more sources

Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression [PDF]

The Journal of Clinical Investigation
Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key ...
Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A. Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye   +23 more
doaj   +2 more sources