scholarly journals Arginine Methylation in Brain Tumors: Tumor Biology and Therapeutic Strategies

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 124
Author(s):  
Jean-Paul Bryant ◽  
John Heiss ◽  
Yeshavanth Kumar Banasavadi-Siddegowda
Keyword(s):  
Brain Tumors ◽  
Cancer Biology ◽  
Metabolic Diseases ◽  
Tumor Biology ◽  
Arginine Methylation ◽  
Post Translational Modification ◽  
Cellular Regulation ◽  
Aberrant Expression ◽  
Arginine Residues ◽  
Protein Arginine Methylation

Protein arginine methylation is a common post-translational modification that plays a pivotal role in cellular regulation. Protein arginine methyltransferases (PRMTs) catalyze the modification of target proteins by adding methyl groups to the guanidino nitrogen atoms of arginine residues. Protein arginine methylation takes part in epigenetic and cellular regulation and has been linked to neurodegenerative diseases, metabolic diseases, and tumor progression. Aberrant expression of PRMTs is associated with the development of brain tumors such as glioblastoma and medulloblastoma. Identifying PRMTs as plausible contributors to tumorigenesis has led to preclinical and clinical investigations of PRMT inhibitors for glioblastoma and medulloblastoma therapy. In this review, we discuss the role of arginine methylation in cancer biology and provide an update on the use of small molecule inhibitors of PRMTs to treat glioblastoma, medulloblastoma, and other cancers.

scholarly journals Arginine methylation helps SepIVA balance regulation of septation and elongation in Mycobacterium smegmatis

2021 ◽  
Author(s):  
Angela H Freeman ◽  
Karen Tembiwa ◽  
James R Brenner ◽  
Michael R Chase ◽  
Sarah M Fortune ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Smegmatis ◽  
Physiological Role ◽  
Arginine Methylation ◽  
Post Translational Modification ◽  
Polar Localization ◽  
Division Factor ◽  
Protein Arginine Methylation ◽  
First Time

AbstractGrowth of mycobacterial cells requires successful coordination between elongation and division of the cell wall. However, it is not clear which factors directly mediate this coordination. Here, we studied the function and post-translational modification of an essential division factor, SepIVA, in Mycobacterium smegmatis. We find that SepIVA is arginine methylated, and that these modifications alter both division and polar elongation of Msmeg. Furthermore, SepIVA impacts the localization of MurG. Polar localization of MurG correlates with polar elongation in arginine methylation mutants of sepIVA. These results establish SepIVA as a regulator of both elongation and division, and characterize a physiological role for protein arginine methylation for the first time in bacteria.

Biochemical and Computational Approaches for the Large-Scale Analysis of Protein Arginine Methylation by Mass Spectrometry

2020 ◽  
Vol 21 (7) ◽  
pp. 725-739
Author(s):  
Daniele Musiani ◽  
Enrico Massignani ◽  
Alessandro Cuomo ◽  
Avinash Yadav ◽  
Tiziana Bonaldi
Keyword(s):  
Mass Spectrometry ◽  
Large Scale ◽  
High Resolution Mass Spectrometry ◽  
Arginine Methylation ◽  
Research Field ◽  
Scale Analysis ◽  
Post Translational Modification ◽  
Large Scale Analysis ◽  
Protein Arginine Methylation

: The absence of efficient mass spectrometry-based approaches for the large-scale analysis of protein arginine methylation has hindered the understanding of its biological role, beyond the transcriptional regulation occurring through histone modification. In the last decade, however, several technological advances of both the biochemical methods for methylated polypeptide enrichment and the computational pipelines for MS data analysis have considerably boosted this research field, generating novel insights about the extent and role of this post-translational modification. : Here, we offer an overview of state-of-the-art approaches for the high-confidence identification and accurate quantification of protein arginine methylation by high-resolution mass spectrometry methods, which comprise the development of both biochemical and bioinformatics methods. The further optimization and systematic application of these analytical solutions will lead to ground-breaking discoveries on the role of protein methylation in biological processes.

scholarly journals Identification of hnRNP-A1 as a pharmacodynamic biomarker of type I PRMT inhibition in blood and tumor tissues

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Paul B. Noto ◽  
Timothy W. Sikorski ◽  
Francesca Zappacosta ◽  
Craig D. Wagner ◽  
Rocio Montes de Oca ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Arginine Methylation ◽  
Regulation Of Transcription ◽  
Type I ◽  
Hnrnp A1 ◽  
Post Translational Modification ◽  
Peripheral Blood Mononuclear ◽  
Proteomic Approach ◽  
Arginine Residues

AbstractArginine methylation has been recognized as a post-translational modification with pleiotropic effects that span from regulation of transcription to metabolic processes that contribute to aberrant cell proliferation and tumorigenesis. This has brought significant attention to the development of therapeutic strategies aimed at blocking the activity of protein arginine methyltransferases (PRMTs), which catalyze the formation of various methylated arginine products on a wide variety of cellular substrates. GSK3368715 is a small molecule inhibitor of type I PRMTs currently in clinical development. Here, we evaluate the effect of type I PRMT inhibition on arginine methylation in normal human peripheral blood mononuclear cells and utilize a broad proteomic approach to identify type I PRMT substrates. This work identified heterogenous nuclear ribonucleoprotein A1 (hnRNP-A1) as a pharmacodynamic biomarker of type I PRMT inhibition. Utilizing targeted mass spectrometry (MS), methods were developed to detect and quantitate changes in methylation of specific arginine residues on hnRNP-A1. This resulted in the development and validation of novel MS and immune assays useful for the assessment of GSK3368715 induced pharmacodynamic effects in blood and tumors that can be applied to GSK3368715 clinical trials.

scholarly journals The Role of Protein Arginine Methylation as Post-Translational Modification on Actin Cytoskeletal Components in Neuronal Structure and Function

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1079
Author(s):  
Britta Qualmann ◽  
Michael M. Kessels
Keyword(s):  
Actin Filament ◽  
Regulatory Mechanism ◽  
De Novo ◽  
Arginine Methylation ◽  
Loss Of Function ◽  
Filament Formation ◽  
Post Translational Modification ◽  
Neuronal Structure ◽  
Actin Nucleation ◽  
Protein Arginine Methylation

The brain encompasses a complex network of neurons with exceptionally elaborated morphologies of their axonal (signal-sending) and dendritic (signal-receiving) parts. De novo actin filament formation is one of the major driving and steering forces for the development and plasticity of the neuronal arbor. Actin filament assembly and dynamics thus require tight temporal and spatial control. Such control is particularly effective at the level of regulating actin nucleation-promoting factors, as these are key components for filament formation. Arginine methylation represents an important post-translational regulatory mechanism that had previously been mainly associated with controlling nuclear processes. We will review and discuss emerging evidence from inhibitor studies and loss-of-function models for protein arginine methyltransferases (PRMTs), both in cells and whole organisms, that unveil that protein arginine methylation mediated by PRMTs represents an important regulatory mechanism in neuritic arbor formation, as well as in dendritic spine induction, maturation and plasticity. Recent results furthermore demonstrated that arginine methylation regulates actin cytosolic cytoskeletal components not only as indirect targets through additional signaling cascades, but can also directly control an actin nucleation-promoting factor shaping neuronal cells—a key process for the formation of neuronal networks in vertebrate brains.

scholarly journals Protein arginine methyltransferases: promising targets for cancer therapy

2021 ◽  
Author(s):  
Jee Won Hwang ◽  
Yena Cho ◽  
Gyu-Un Bae ◽  
Su-Nam Kim ◽  
Yong Kee Kim
Keyword(s):  
Cell Cycle ◽  
Cancer Therapy ◽  
Phase 1 ◽  
Cell Types ◽  
Arginine Methylation ◽  
Protein Methylation ◽  
Post Translational Modification ◽  
Nonhistone Proteins ◽  
Protein Arginine Methyltransferases ◽  
Protein Arginine Methylation

AbstractProtein methylation, a post-translational modification (PTM), is observed in a wide variety of cell types from prokaryotes to eukaryotes. With recent and rapid advancements in epigenetic research, the importance of protein methylation has been highlighted. The methylation of histone proteins that contributes to the epigenetic histone code is not only dynamic but is also finely controlled by histone methyltransferases and demethylases, which are essential for the transcriptional regulation of genes. In addition, many nonhistone proteins are methylated, and these modifications govern a variety of cellular functions, including RNA processing, translation, signal transduction, DNA damage response, and the cell cycle. Recently, the importance of protein arginine methylation, especially in cell cycle regulation and DNA repair processes, has been noted. Since the dysregulation of protein arginine methylation is closely associated with cancer development, protein arginine methyltransferases (PRMTs) have garnered significant interest as novel targets for anticancer drug development. Indeed, several PRMT inhibitors are in phase 1/2 clinical trials. In this review, we discuss the biological functions of PRMTs in cancer and the current development status of PRMT inhibitors in cancer therapy.

Opiophobia in Cancer Biology- Justified? - The Role of Perioperative Use of Opioids in Cancer Recurrence

2019 ◽  
Vol 25 (28) ◽  
pp. 3020-3027 ◽  
Author(s):  
Mir W. Sekandarzad ◽  
Chris Doornebal ◽  
Markus W. Hollmann
Keyword(s):  
Pain Management ◽  
Cancer Biology ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Standard Of Care ◽  
Cancer Surgery ◽  
Perioperative Pain Management ◽  
Tumor Growth And Metastasis

: Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. : The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis. : This narrative review highlights earlier and more recent in vitro, in vivo and human retrospective studies that yield conflicting results as to the immune-modulatory effects of morphine on tumor biology. The article examines and explains the discrepancies with regards to the seemingly opposite results of morphine in the tumor milieu. The results of both, earlier studies that demonstrated procarcinogenic effects versus the data of more recent refined rodent studies that yielded neutral or even anti-carcinogenic effects are presented here. : Until the results of prospective randomized controlled trials are available to clarify this important question, it is currently not warranted to support opiophobia and opioids continue to constitute a pivotal role in the pain management of cancer patients.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Protein Methylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Regulatory Enzymes ◽  
Lysine Residues ◽  
Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

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