Histone Mono-Ubiquitination in Transcriptional Regulation and Its Mark on Life: Emerging Roles in Tissue Development and Disease

Oss-Ronen, Liat; Sarusi, Tzlil; Cohen, Idan

doi:10.3390/cells11152404

Cited by 26 publications

(19 citation statements)

References 228 publications

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“…High levels of expression of Polycomb repressive DUB complex (PR–DUB) in zygotes can rapidly reduce H2AK119ub levels, resulting in developmental arrest at the 4‐cell stage. 859 Furthermore, Cbls play a role in promoting the ubiquitination and degradation of FLT3, which results in the inhibition of FLT3 signaling and limits the development of CD8α + /CD103 + DC1 (cDC1). When Cbls are absent, activated FLT3 cannot be efficiently removed, leading to constant FLT3 signaling that favors cDC1 development and expansion.…”

Section: Ubiquitinationmentioning

confidence: 99%

“…It has been demonstrated that PRC1, in conjunction with H2AK119ub, influences early embryonic development. High levels of expression of Polycomb repressive DUB complex (PR–DUB) in zygotes can rapidly reduce H2AK119ub levels, resulting in developmental arrest at the 4‐cell stage 859 . Furthermore, Cbls play a role in promoting the ubiquitination and degradation of FLT3, which results in the inhibition of FLT3 signaling and limits the development of CD8α + /CD103 + DC1 (cDC1).…”

Section: Ubiquitinationmentioning

confidence: 99%

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Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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Section: Ubiquitinationmentioning

confidence: 99%

Section: Ubiquitinationmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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“…Among core histones, mono-ubiquitination prevalently exists and plays a core role in cellular DNA damage [ 67 ]. A sequential enzymatic reaction induces the occurrence of mono-ubiquitination: ubiquitin is first activated by a ubiquitin-activating enzyme(E1) in an ATP-dependent manner, then binds to cysteine residues on a ubiquitin-conjugating enzyme (E2) by a thioester bond, and finally, ubiquitin in E2 is transferred to a target lysine site in the histone by RING finger ubiquitin ligase E3 [ 68 ]. Histone H2A lysine 119 mono-ubiquitination (H2AK119ub) and H2BK120ub are the two major histone mono-ubiquitination events [ 68 ].…”

Section: Histone Modifications In Sepsismentioning

confidence: 99%

Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification

Shi

Zhang

et al. 2023

Cell Death Dis

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Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation and immunosuppression is a crucial feature of sepsis immunity. Epigenetic modifications, including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNA, play essential roles in regulating sepsis immunity through epi-information independent of the DNA sequence. In recent years, the mechanisms of histone modification in sepsis have received increasing attention, with ongoing discoveries of novel types of histone modifications. Due to the capacity for prolonged effects on immune cells, histone modifications can induce immune cell reprogramming and participate in the long-term immunosuppressed state of sepsis. Herein, we systematically review current mechanisms of histone modifications involved in the regulation of sepsis, summarize their role in sepsis from an immune perspective and provide potential therapeutic opportunities targeting histone modifications in sepsis treatment.

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“…Ubiquitination is usually observed in H2A at lysine 119 (H2AK119ub1) and H2B at lysine 120 (H2B K120ub1). H2A ubiquitination is associated predominantly with transcriptional repression and considered a repressive mark, whereas H2B ubiquitination appears to be involved both in transcriptional activation and gene silencing [ 30 , 31 ]. ( Figure 1 ).…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Empowering the Potential of CAR-T Cell Immunotherapies by Epigenetic Reprogramming

Alvanou

Lysandrou

Christophi

et al. 2023

Cancers

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T-cell-based, personalized immunotherapy can nowadays be considered the mainstream treatment for certain blood cancers, with a high potential for expanding indications. Chimeric antigen receptor T cells (CAR-Ts), an ex vivo genetically modified T-cell therapy product redirected to target an antigen of interest, have achieved unforeseen successes in patients with B-cell hematologic malignancies. Frequently, however, CAR-T cell therapies fail to provide durable responses while they have met with only limited success in treating solid cancers because unique, unaddressed challenges, including poor persistence, impaired trafficking to the tumor, and site penetration through a hostile microenvironment, impede their efficacy. Increasing evidence suggests that CAR-Ts’ in vivo performance is associated with T-cell intrinsic features that may be epigenetically altered or dysregulated. In this review, we focus on the impact of epigenetic regulation on T-cell differentiation, exhaustion, and tumor infiltration and discuss how epigenetic reprogramming may enhance CAR-Ts’ memory phenotype, trafficking, and fitness, contributing to the development of a new generation of potent CAR-T immunotherapies.

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Histone Mono-Ubiquitination in Transcriptional Regulation and Its Mark on Life: Emerging Roles in Tissue Development and Disease

Cited by 26 publications

References 228 publications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification

Empowering the Potential of CAR-T Cell Immunotherapies by Epigenetic Reprogramming

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