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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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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. |
format | Online Article Text |
id | pubmed-10654028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
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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