Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells

Liu, Peng; Shuaib, Muhammad; Zhang, Huoming; Nadeef, Seba

doi:10.1186/s13072-019-0322-5

Cited by 18 publications

(9 citation statements)

References 30 publications

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“…Within the PRC2 complex, EZH2 (and to a lesser extent, EZH1) is the catalytic subunit responsible for methyltransferase activity. Both EZH proteins were observed to be phosphorylated, although EZH1 phosphorylation was shown to lead to degradation, while EZH2 phosphorylation led to reduced function (2,3). PRC2 mediates di-and trimethylation of histone 3 lysine 27 (H3K27), which is classified as a transcriptionally repressive mark while acetylation at this same residue is regarded as permissive for active transcription, making H3K27 post-translational modification status an important regulator of the cellular transcriptome (4).…”

Section: Introductionmentioning

confidence: 99%

EZH2 as a Regulator of CD8+ T Cell Fate and Function

2020

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Enhancer of zeste 2 (EZH2) is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) that mediates di-and trimethylation of histone 3 lysine 27 effectively precluding successful gene transcription at these loci. This class of epigenetic modifications facilitates the maintenance of tissue-specific cellular transcriptional programs as cells undergoing successive rounds of proliferation. CD8+ T cells are effective mediators of adaptive immunity and function to eliminate virus-and bacteria-infected cells as well as tumor cells. Upon recognition of cognate antigen, T cells undergo activation/proliferation to clear the target cells. The heterogeneous population of responding T cells formed during these proliferative events thus rely on epigenetic modifications to ensure identity and confer functional capabilities. In this review, we will focus on the role of the dynamic expression EZH2 in shaping the epigenetic landscape of CD8+ T cell fate and function, with a particular emphasis on infection and cancer. We also explore competing hypotheses pertaining to EZH2 function and the prospects of clinical EZH2 inhibitors in fine-tuning T cell responses.

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Section: Introductionmentioning

confidence: 99%

EZH2 as a Regulator of CD8+ T Cell Fate and Function

2020

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“…However, there are differences among them. The phosphorylation of EZH1 results in its degradation and significantly diminishes its function [ 24 , 25 ]. The regulatory impact of EZH2 on other genes is related to its impact on histone H3 lysine 27 (H3K27me3).…”

Section: Ezh2 Signaling In Cancermentioning

confidence: 99%

The long and short non-coding RNAs modulating EZH2 signaling in cancer

et al. 2022

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Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.

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“…The MS analysis was performed as described previously 73,74 with slight modifications. For mass spectrometry analysis an Orbitrap Fusion mass spectrometer (MS) (Lumos, Thermo Fisher Scientific) was used in data-dependent acquisition (DDA) mode.…”

Section: Methodsmentioning

confidence: 99%

Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

Mourier

Shuaib

Hala

et al. 2021

Preprint

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Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.

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Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells

Cited by 18 publications

References 30 publications

EZH2 as a Regulator of CD8+ T Cell Fate and Function

EZH2 as a Regulator of CD8+ T Cell Fate and Function

The long and short non-coding RNAs modulating EZH2 signaling in cancer

Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients

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