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O-GlcNAc has crosstalk with ADP-ribosylation via PARG

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relatio...

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Autores principales: Li, Jie, Liu, Xiangxiang, Peng, Bin, Feng, Tingting, Zhou, Wen, Meng, Li, Zhao, Shanshan, Zheng, Xiyuan, Wu, Chen, Wu, Shian, Chen, Xing, Xu, Xingzhi, Sun, Jianwei, Li, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654028/
https://www.ncbi.nlm.nih.gov/pubmed/37858678
http://dx.doi.org/10.1016/j.jbc.2023.105354
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author Li, Jie
Liu, Xiangxiang
Peng, Bin
Feng, Tingting
Zhou, Wen
Meng, Li
Zhao, Shanshan
Zheng, Xiyuan
Wu, Chen
Wu, Shian
Chen, Xing
Xu, Xingzhi
Sun, Jianwei
Li, Jing
author_facet Li, Jie
Liu, Xiangxiang
Peng, Bin
Feng, Tingting
Zhou, Wen
Meng, Li
Zhao, Shanshan
Zheng, Xiyuan
Wu, Chen
Wu, Shian
Chen, Xing
Xu, Xingzhi
Sun, Jianwei
Li, Jing
author_sort Li, Jie
collection PubMed
description O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relationship with ADP-ribosylation, which involves decorating target proteins with the ADP-ribose moiety. We discovered that the poly(ADP-ribosyl)ation “eraser”, ADP-ribose glycohydrolase (PARG), is O-GlcNAcylated at Ser26, which is in close proximity to its nuclear localization signal. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen (PCNA). In hepatocellular carcinoma (HCC) cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 (DDB1) and attenuates its auto-ubiquitination, thereby stabilizing DDB1 and allowing it to degrade its downstream targets, such as c-Myc. We further demonstrated that PARG-S26A, the O-GlcNAc-deficient mutant, promoted HCC in mouse xenograft models. Our findings thus reveal that PARG O-GlcNAcylation inhibits HCC, and we propose that O-GlcNAc glycosylation may crosstalk with many other PTMs.
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spelling pubmed-106540282023-10-17 O-GlcNAc has crosstalk with ADP-ribosylation via PARG Li, Jie Liu, Xiangxiang Peng, Bin Feng, Tingting Zhou, Wen Meng, Li Zhao, Shanshan Zheng, Xiyuan Wu, Chen Wu, Shian Chen, Xing Xu, Xingzhi Sun, Jianwei Li, Jing J Biol Chem Research Article O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relationship with ADP-ribosylation, which involves decorating target proteins with the ADP-ribose moiety. We discovered that the poly(ADP-ribosyl)ation “eraser”, ADP-ribose glycohydrolase (PARG), is O-GlcNAcylated at Ser26, which is in close proximity to its nuclear localization signal. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen (PCNA). In hepatocellular carcinoma (HCC) cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 (DDB1) and attenuates its auto-ubiquitination, thereby stabilizing DDB1 and allowing it to degrade its downstream targets, such as c-Myc. We further demonstrated that PARG-S26A, the O-GlcNAc-deficient mutant, promoted HCC in mouse xenograft models. Our findings thus reveal that PARG O-GlcNAcylation inhibits HCC, and we propose that O-GlcNAc glycosylation may crosstalk with many other PTMs. American Society for Biochemistry and Molecular Biology 2023-10-17 /pmc/articles/PMC10654028/ /pubmed/37858678 http://dx.doi.org/10.1016/j.jbc.2023.105354 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Li, Jie
Liu, Xiangxiang
Peng, Bin
Feng, Tingting
Zhou, Wen
Meng, Li
Zhao, Shanshan
Zheng, Xiyuan
Wu, Chen
Wu, Shian
Chen, Xing
Xu, Xingzhi
Sun, Jianwei
Li, Jing
O-GlcNAc has crosstalk with ADP-ribosylation via PARG
title O-GlcNAc has crosstalk with ADP-ribosylation via PARG
title_full O-GlcNAc has crosstalk with ADP-ribosylation via PARG
title_fullStr O-GlcNAc has crosstalk with ADP-ribosylation via PARG
title_full_unstemmed O-GlcNAc has crosstalk with ADP-ribosylation via PARG
title_short O-GlcNAc has crosstalk with ADP-ribosylation via PARG
title_sort o-glcnac has crosstalk with adp-ribosylation via parg
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654028/
https://www.ncbi.nlm.nih.gov/pubmed/37858678
http://dx.doi.org/10.1016/j.jbc.2023.105354
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