Emerging Roles of RNF168 in Tumor Progression

Xie, Tianyuan; Qin, Hai; Yuan, Zheng‐Dong; Zhang, Yiwen; Li, Xiaoman; Zheng, Lufeng

doi:10.3390/molecules28031417

Cited by 7 publications

(5 citation statements)

References 84 publications

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“…However, UbcH5c barely makes contact with the nucleosomal histone surface, and the lack of specific interactions between UbcH5c and the substrate may allow UbcH5c to efficiently ubiquitinate multiple substrates by pairing with different E3 ligases (e.g., RNF168 6 , Ring1B/Bmi1 55 and BRCA1/BARD1 56 ). Previous studies have suggested that the histone H2A α1 extension helix (16)(17)(18)(19)(20)(21)(22) plays a critical role in RNF168 activity 22 , whereas we did not observe direct engagement of UbcH5c with this helix in our structures.…”

Section: Interactions Of Ubch5c and Nucleosomal Dnacontrasting

confidence: 95%

“…Dysfunction or mutations of RNF168 have been strongly implicated in the development and progression of various human diseases, including tumours such as breast and esophageal cancers 16 , as well as RIDDLE syndrome 17 , a novel human immunodeficiency and radiosensitivity disorder associated with defective DNA double-strand break repair. Consequently, mechanistic studies targeting RNF168 ubiquitination have garnered significant attention due to their profound biological and clinical implications 18,19 .…”

Section: Introductionmentioning

confidence: 99%

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Capturing Snapshots of Nucleosomal H2A K13/K15 Ubiquitination Mediated by the Monomeric E3 Ligase RNF168

Ai,

Tong,

Deng

et al. 2024

Preprint

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AbstractsThe DNA damage repair regulatory protein RNF168, a monomeric RING-type E3 ligase, plays a crucial role in regulating cell fate and DNA repair by specific and efficient ubiquitination of the adjacent Lys13 and Lys15 sites at the H2A N-terminal tail. However, understanding how RNF168 coordinates with its cognate E2 enzyme UbcH5c to ubiquitinate H2AK13/15 site-specifically has long been hampered by the lack of high-resolution structures of RNF168 and UbcH5c∼Ub in complex with nucleosomes. Here, we developed mechanism-based chemical trapping strategies and determined the cryo-EM structures of the RNF168/UbcH5c–Ub/NCP complex captured in transient H2AK13/15 monoubiquitination and adjacent dual-monoubiquitination reactions. Our structural analysis revealed that RNF168 stably binds to the nucleosomal H2A–H2B acidic patch through a basic helix with multiple interactions, which positions the UbcH5c active centre directly over the H2A N-terminus, providing a “helix-anchoring” mode for monomeric E3 ligase RNF168 on nucleosome in contrast to the “compass-binding” mode of dimeric E3 ligases. Furthermore, our chemically synthesized ubiquitinated histones have enabled the elucidation of the efficiency of Ub installation and the interplay between the initial and subsequent Ub modifications on the adjacent H2A K13 and K15 sites. Overall, our work not only provides structural snapshots of H2A K13/K15 site-specific monoubiquitination and adjacent dual-monoubiquitination, but also offers a near-atomic resolution structural framework for understanding how pathogenic mutations or physiological modifications affect the molecular function of RNF168 in H2A K13/15 ubiquitination.

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Section: Interactions Of Ubch5c and Nucleosomal Dnacontrasting

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Capturing Snapshots of Nucleosomal H2A K13/K15 Ubiquitination Mediated by the Monomeric E3 Ligase RNF168

Ai,

Tong,

Deng

et al. 2024

Preprint

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“…It is not uniform that the distribution of lipophilic monomer, hydrophilic monomers along the polymer chain. 35 The morphology and polymerization process of other selfpolishing resin emulsions are the same.…”

Section: Analysis Of Latex Particle Morphology and Polymerization Pro...mentioning

confidence: 99%

Preparation and application of the water‐based acrylic self‐polishing resin: Good storage stability, good film‐forming matrix of marine antifouling coatings

Liu,

Wei

et al. 2024

J of Applied Polymer Sci

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In order to reduce the release of volatile organic compounds (VOCs), it is of great practical significance to develop water‐based self‐polishing antifouling coatings instead of traditional acrylic self‐polishing antifouling coatings. However, when preparing film forming matrix resin emulsions for water‐based antifouling coatings, the use of emulsifiers in large amounts causes film‐forming defects and poor adhesion. Herein, soap‐free emulsion polymerization is utilized to prepare resin emulsions by copolymerization of hydrophilic monomers, lipophilic monomers and polymerizable hydrophilic ionic monomers. The hydrophilic structure can give the water‐based polymer self‐emulsification function to maintain the stability of the emulsion and can promote the fusion between the latex particles by forming hydrogen bonds and coordination bonds, and its connection with the pigments and fillers in the coating can also promote the excellent film formation of the coating. The experimental results show that the water‐based self‐polishing antifouling resin emulsion has good storage stability and compatibility with the pigments and fillers. The coatings formulated using this emulsion as the film‐forming matrix firmly adhered to substrates and displayed satisfactory antifouling performance even after being exposed to a real sea environment for 18 months. This study presents a simple approach for the development of water‐based resin emulsion with good storage stability and good water‐based self‐polishing marine antifouling coatings.

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“…RNF168 has another role downstream of DDR in DSB repair by substituting for BRCA1 in BRCA1 and 53BP1 null cells [ 71 , 74 ]. High RNF168 expression levels have been observed in breast cancer and esophageal cancer [ 75 , 76 ], as well as genetic alterations in human papilloma virus (HPV)-positive head and neck cancer [ 77 ]. It is also commonly discussed concerning PARPi resistance [ 71 , 78 ].…”

Section: E3 Ligases As Novel Targetsmentioning

confidence: 99%

RNF126, 168 and CUL1: The Potential Utilization of Multi-Functional E3 Ubiquitin Ligases in Genome Maintenance for Cancer Therapy

Chang

2023

Biomedicines

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Ubiquitination is a post-translational modification (PTM) that is involved in proteolysis, protein–protein interaction, and signal transduction. Accumulation of mutations and genomic instability are characteristic of cancer cells, and dysfunction of the ubiquitin pathway can contribute to abnormal cell physiology. Because mutations can be critical for cells, DNA damage repair, cell cycle regulation, and apoptosis are pathways that are in close communication to maintain genomic integrity. Uncontrolled cell proliferation due to abnormal processes is a hallmark of cancer, and mutations, changes in expression levels, and other alterations of ubiquitination factors are often involved. Here, three E3 ubiquitin ligases will be reviewed in detail. RNF126, RNF168 and CUL1 are involved in DNA damage response (DDR), DNA double-strand break (DSB) repair, cell cycle regulation, and ultimately, cancer cell proliferation control. Their involvement in multiple cellular pathways makes them an attractive candidate for cancer-targeting therapy. Functional studies of these E3 ligases have increased over the years, and their significance in cancer is well reported. There are continuous efforts to develop drugs targeting the ubiquitin pathway for anticancer therapy, which opens up the possibility for these E3 ligases to be evaluated for their potential as a target protein for anticancer therapy.

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Emerging Roles of RNF168 in Tumor Progression

Cited by 7 publications

References 84 publications

Capturing Snapshots of Nucleosomal H2A K13/K15 Ubiquitination Mediated by the Monomeric E3 Ligase RNF168

Capturing Snapshots of Nucleosomal H2A K13/K15 Ubiquitination Mediated by the Monomeric E3 Ligase RNF168

Preparation and application of the water‐based acrylic self‐polishing resin: Good storage stability, good film‐forming matrix of marine antifouling coatings

RNF126, 168 and CUL1: The Potential Utilization of Multi-Functional E3 Ubiquitin Ligases in Genome Maintenance for Cancer Therapy

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