H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis

Zhang, Xian; Li, Binkui; Rezaeian, Abdol Hossein; Xu, Xiaohong; Chou, Ping-Chieh; Jin, Guoxiang; Han, Fei; Pan, Bo; Wang, Chi-Yun; Long, Jie; Zhang, Anmei; Huang, Chih‐Yang; Tsai, Fuu Jen; Tsai, Chang Hai; Logothetis, Christopher J.; Lin, Hui Kuan

doi:10.1038/ncomms14799

Cited by 38 publications

(23 citation statements)

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“…26 Histone H3 ubiquitination by NEDD4 regulated H3 acetylation and tumorigenesis. 27 NEDD4 directly binds to and polyubiquitinates PTEN, leading to its proteasomal degradation. 15 Depletion of NEDD4 in DU145 cells with PTEN-positive caused a clear inhibition of tumor growth in nude mice, whereas depletion of NEDD4 in PC3 cells with PTEN-negative had no effect on tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells

Wen

Wang

et al. 2017

Cell Cycle

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The neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) plays a pivotal oncogenic role in various types of human cancers. However, the function of NEDD4 in bladder cancer has not been fully investigated. In the present study, we aim to explore whether NEDD4 governs cell proliferation, apoptosis, migration, and invasion in bladder cancer cells. Our results showed that downregulation of NEDD4 suppressed cell proliferation in bladder cancer cells. Moreover, we found that inhibition of NEDD4 significantly induced cell apoptosis. Furthermore, downregulation of NEDD4 retarded cell migration and invasion. Notably, overexpression of NEDD4 enhanced cell growth and inhibited apoptosis. Consistently, upregulation of NEDD4 promoted cell migration and invasion in bladder cancer cells. Mechanically, our Western blotting results revealed that downregulation of NEDD4 activated PTEN and inhibited Notch-1 expression, whereas upregulation of NEDD4 reduced PTEN level and increased Notch-1 level in bladder cancer cells. Our findings indicated that NEDD4 exerts its oncogenic function partly due to regulation of PTEN and Notch-1 in bladder cancer cells. These results further revealed that targeting NEDD4 could be a useful approach for the treatment of bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells

Wen

Wang

et al. 2017

Cell Cycle

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“…Similarly to histone phosphorylation, there is also cross-talk between histone ubiquitination and other histone modifications [ 46 – 48 ]. For instance, monoubiquitination of histone H3 is able to induce acetylation of the same histone [ 49 ].…”

Section: Main Textmentioning

confidence: 99%

Histone modifications and their role in epigenetics of atopy and allergic diseases

Alhamwe

Khalaila

Wolf

et al. 2018

Allergy Asthma Clin Immunol

166

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This review covers basic aspects of histone modification and the role of posttranslational histone modifications in the development of allergic diseases, including the immune mechanisms underlying this development. Together with DNA methylation, histone modifications (including histone acetylation, methylation, phosphorylation, ubiquitination, etc.) represent the classical epigenetic mechanisms. However, much less attention has been given to histone modifications than to DNA methylation in the context of allergy. A systematic review of the literature was undertaken to provide an unbiased and comprehensive update on the involvement of histone modifications in allergy and the mechanisms underlying this development. In addition to covering the growing interest in the contribution of histone modifications in regulating the development of allergic diseases, this review summarizes some of the evidence supporting this contribution. There are at least two levels at which the role of histone modifications is manifested. One is the regulation of cells that contribute to the allergic inflammation (T cells and macrophages) and those that participate in airway remodeling [(myo-) fibroblasts]. The other is the direct association between histone modifications and allergic phenotypes. Inhibitors of histone-modifying enzymes may potentially be used as anti-allergic drugs. Furthermore, epigenetic patterns may provide novel tools in the diagnosis of allergic disorders.

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“…Epigenetic traits are tightly regulated by the major epigenetic modification: histone proteins associated with DNA (histone modifications). Histones may undergo divergent epigenetic changes, including methylation, acetylation, phosphorylation, ubiquitylation and SUMOylation, which are often involved in establishing patterns of gene dysregulation associated with altered chromatin states, leading to gene activation and gene silencing in a host of diseases [ 109 – 111 ]. In this part, we particularly focus on the latest advances in the field of the histones modifications profiles associated with the regulation of macrophages polarization to M1 or M2 phenotypes.…”

Section: Histone Modificationmentioning

confidence: 99%

Promising landscape for regulating macrophage polarization: epigenetic viewpoint

et al. 2017

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Macrophages are critical myeloid cells with the hallmark of phenotypic heterogeneity and functional plasticity. Macrophages phenotypes are commonly described as classically-activated M1 and alternatively-activated M2 macrophages which play an essential role in the tissues homeostasis and diseases pathogenesis. Alternations of macrophage polarization and function states require precise regulation of target-gene expression. Emerging data demonstrate that epigenetic mechanisms and transcriptional factors are becoming increasingly appreciated in the orchestration of macrophage polarization in response to local environmental signals. This review is to focus on the advanced concepts of epigenetics changes involved with the macrophage polarization, including microRNAs, DNA methylation and histone modification, which are responsible for the altered cellular signaling and signature genes expression during M1 or M2 polarization. Eventually, the persistent investigation and understanding of epigenetic mechanisms in tissue macrophage polarization and function will enhance the potential to develop novel therapeutic targets for various diseases.

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H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis

Cited by 38 publications

References 50 publications

Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells

Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells

Histone modifications and their role in epigenetics of atopy and allergic diseases

Promising landscape for regulating macrophage polarization: epigenetic viewpoint

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