Ras-AKT signaling represses the phosphorylation of histone H1.5 at threonine 10 via GSK3 to promote the progression of glioma

Sang, Ben; Sun, Jianjing; Yang, Dongxu; Xu, Zhen; Wei, Yuzhen

doi:10.1080/21691401.2019.1638795

Cited by 9 publications

(11 citation statements)

References 38 publications

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“…For example, Liu et al and Li et al indicated that Ras-PI3K pathway activation could reduce the acetylation of histone H3 at lysine 56 (H3 K56ac ) and then promote the proliferation and migration of HeLa cells, as well as the occurrence and development of uveal melanoma [29,30]. Moreover, Sang et al discovered that Ras-AKT pathway activation could inhibit the phosphorylation of histone H1.5 at threonine 10 (H1.5 T10ph ) and then promote the development of glioma [31]. We could propose that Ras-PI3K-AKT pathway activation might take part in the regulation of the number of histone modifications in cancer cells, which may form a very intricate regulatory Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Ras-PI3K pathway aberrant activation plays an important role in the occurrence and development of osteosarcoma. This study investigated the functions of Ras-PI3K pathway specific activation on histone H2A phosphorylation at threonine 120 (H2A T120ph) in osteosarcoma cells, along with the possible internal molecular mechanisms. Methods: Cell transfection was done to alter Ras G12V/Y40C , H2A T120ph and vaccinia-related kinase 1 (VRK1) expression. Then, cell viability, proliferation, migration and cell cycle distribution were assessed, respectively. qRT-PCR was utilized to measure the VRK1 and Ras-PI3K pathway downstream genes (CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16) expression. Chromatin immunoprecipitation (ChIP) was conducted to evaluate the input levels of H2A T120ph and VRK1 in the promoter regions of Ras-PI3K pathway downstream genes. Results: Ras-PI3K specific activation promoted histone H2A T120ph. H2A T120ph participated in the oncogenic functions of Ras-PI3K pathway on osteosarcoma by modulating the transcription of Ras-PI3K-targeted genes. Moreover, VRK1 contributed to the Ras-PI3K specific activation-induced up-regulation of H2A T120ph and osteosarcoma progression. Ras-PI3K pathway-specific activation-induced up-regulation of H2A T120ph was achieved by up-regulation of VRK1. Conclusions: Ras-PI3K pathway activation promoted osteosarcoma progression might be via up-regulating VRK1-mediated H2A T120ph. We proposed that VRK1 and H2A T120ph could be the potential targets for osteosarcoma diagnosis and treatment. HIGHLIGHTS 1. H2A T120ph is specifically promoted by Ras-PI3K pathway activation. 2. H2A T120ph joins in the oncogenic effects of Ras-PI3K pathway on osteosarcoma. 3. H2A T120ph regulates the transcription of Ras-PI3K-targeted genes. 4. VRK1 takes part in the regulatory function of Ras-PI3K pathway on H2A T120ph .

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Section: Discussionmentioning

confidence: 99%

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…That would require a detailed molecular analysis of the chromatin alterations/epigenetic modifications occurring at the H1.5 promoter. The epigenetic changes and protein interactions occurring on the HIST1 locus in general, are usually omitted in studies investigating H1.5 expression [ 10 , 16 , 20 , 21 ]. Therefore, the connections of H1.5 expression to cellular processes—differentiation and disease—remain unknown.…”

Section: A Promiscuous Protein—h15’s Many Interaction Partnersmentioning

confidence: 99%

“…That the latter is necessary to experiments involving linker histones has been exemplified by Sang et al . [ 21 ], who investigated the role of site-specific phosphorylation of H1.5 in Ras-mediated glioma progression. As it is currently disputed, whether this paper is lacking scientific integrity, we present the results below but advise the reader to take them as a starting point for thought [ 40 ].…”

Section: Differentiation Gone Wrong—h15’s Role In Cancermentioning

confidence: 99%

“…As it is currently disputed, whether this paper is lacking scientific integrity, we present the results below but advise the reader to take them as a starting point for thought [ 40 ]. The glioblastoma cells expressing a cancerogenic Ras mutant (RasG12V/Y40C), had lower levels of H1.5 phosphorylation at threonine 10 (H1.5T10ph) compared to wildtype-cells [ 21 ]. Furthermore, the mutant cells, exhibited increased cell growth and migration, as well as altered expression levels of Ras target-genes, known to be involved in cancer [ 21 ].…”

Section: Differentiation Gone Wrong—h15’s Role In Cancermentioning

confidence: 99%

“…The glioblastoma cells expressing a cancerogenic Ras mutant (RasG12V/Y40C), had lower levels of H1.5 phosphorylation at threonine 10 (H1.5T10ph) compared to wildtype-cells [ 21 ]. Furthermore, the mutant cells, exhibited increased cell growth and migration, as well as altered expression levels of Ras target-genes, known to be involved in cancer [ 21 ]. The changes in gene expression, cell growth, and ability to migrate were reversed by the overexpression of an H1.5T10ph mimetic [ 21 ].…”

Section: Differentiation Gone Wrong—h15’s Role In Cancermentioning

confidence: 99%

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Linker histone H1.5 is an underestimated factor in differentiation and carcinogenesis

Behrends

Engmann

2020

Environmental Epigenetics

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Human histone H1.5, in mice called H1b, belongs to the family of linker histones (H1), which are key players in chromatin organization. These proteins sit on top of nucleosomes, in part to stabilize them, and recruit core histone modifying enzymes. Through subtype-specific deposition patterns and numerous post-translational modifications, they fine-tune gene expression and chromatin architecture, and help to control cell fate and homeostasis. However, even though it is increasingly implicated in mammalian development, H1.5 has not received as much research attention as its relatives. Recent studies have focused on its prognostic value in cancer patients and its contribution to tumorigenesis through specific molecular mechanisms. However, many functions of H1.5 are still poorly understood. In this review, we will summarize what is currently known about H1.5 and its function in cell differentiation and carcinogenesis. We will suggest key experiments that are required to understand the molecular network, in which H1.5 is embedded. These experiments will advance our understanding of the epigenetic reprogramming occurring in developmental and carcinogenic processes.

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Retraction

et al. 2019

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Bao G, Pan W, Huang J, Zhou T. K‐RasG12V/T35S‐ERK1/2 pathway regulates H2BS14ph through Mst1 to facilitate the advancement of breast cancer cells. BioFactors. 2023;49:202. https://doi.org/10.1002/biof.1589 This article, published online on 28 November 2019 in Wiley Online Library, has been retracted by agreement between the International Union of Biochemistry and Molecular Biology, the Editor in Chief (Dr. Angelo Azzi), and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Evidence for image manipulation was found in figures 1, 4, 5, and 6. As a result, the conclusions of this article are considered to be invalid.

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Ras-AKT signaling represses the phosphorylation of histone H1.5 at threonine 10 via GSK3 to promote the progression of glioma

Abstract: View related articles View Crossmark data Citing articles: 3 View citing articles Ras-AKT signaling represses the phosphorylation of histone H1.5 at threonine 10 via GSK3 to promote the progression of glioma

Cited by 9 publications

References 38 publications

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

Linker histone H1.5 is an underestimated factor in differentiation and carcinogenesis

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