PRMT5-mediated regulation of developmental myelination

Scaglione, Antonella; Patzig, Julia; Liang, Jialiang; Frawley, Rebecca; Bok, Jabez; Mela, Angeliki; Yattah, Camila; Zhang, Jingxian; Teo, Shun Xie; Zhou, Ting; Chen, Shuibing; Bernstein, Emily; Canoll, Peter; Guccione, Ernesto; Casaccia, Patrizia

doi:10.1038/s41467-018-04863-9

Cited by 82 publications

(65 citation statements)

References 69 publications

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“…These findings were further confirmed using either the PRMT5 inhibitor GSK591 or a PRMT5-specific CRISPR/Cas9 lentivirus, suggesting that PRMT5 is more important for survival and differentiation of OPCs than for their proliferation. Mechanistically, the authors determined, using both brain sections of PRMT5 mutant mice and ex-vivo primary cultures of OPCs, that PRMT5 regulates differentiation of OPCs through induced symmetric methylation of H4R3, which precludes acetylation of nearby lysine residues [63].…”

Section: Introductionmentioning

confidence: 99%

Protein arginine methyltransferase 5 (PRMT5) dysregulation in cancer

et al. 2018

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Protein arginine methyltransferases (PRMTs) are known for their ability to catalyze methylation of specific arginine residues in a wide variety of cellular proteins, which are involved in a plethora of processes including signal transduction, transcription, and more recently DNA recombination. All members of the PRMT family can be grouped into three main classes depending on the type of methylation they catalyze. Type I PRMTs induce monomethylation and asymmetric dimethylation, while type II PRMTs catalyze monomethylation and symmetric dimethylation of specific arginine residues. In contrast, type III PRMTs carry out only monomethylation of arginine residues. In this review, we will focus on PRMT5, a type II PRMT essential for viability and normal development, which has been shown to be overexpressed in a wide variety of cancer cell types, owing it to the crucial role it plays in controlling key growth regulatory pathways. Furthermore, the role of PRMT5 in regulating expression and stability of key transcription factors that control normal stem cell function as well as cancer stem cell renewal will be discussed. We will review recent work that shows that through its ability to methylate various cellular proteins, PRMT5 functions as a master epigenetic regulator essential for growth and development, and we will highlight studies that have examined its dysregulation and the effects of its inhibition on cancer cell growth.

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Section: Introductionmentioning

confidence: 99%

Protein arginine methyltransferase 5 (PRMT5) dysregulation in cancer

et al. 2018

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“…PRMT5 is also important for regulating the p53-dependent mechanism of apoptosis (13). Furthermore, PRMT5 modulates p53 function in cell proliferation (42) and tumorigenesis (62), and p53 signaling has important functions in tumorigenesis (63,64). Overall, these results demonstrate that PRMT5 is directly involved in regulating p53 function in cell apoptosis, the cell cycle, survival and proliferation.…”

Section: Sharpin Is a Mediator Of P53mentioning

confidence: 72%

Shank‑associated RH domain interactor signaling in tumorigenesis (Review)

et al. 2020

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Shank-associated RH domain interactor (SHARPIN) is a component of the linear ubiquitin chain activation complex, which is essential for p53 signaling and inflammation. Previous studies have demonstrated that SHARPIN functions in tumor cell survival, growth, invasion and tumorigenesis. These functions include the regulation of p53 proteins via poly-ubiquitination, interaction with a type II protein arginine methyltransferase 5 in melanoma cells, modulating ras-associated protein-1 through p38 and c-Jun N-terminal kinases/c-Jun signaling, and mediating phosphoinositide 3-kinase/AKT signaling via phosphatase and tensin homologue deleted on chromosome 10. Hence, SHARPIN not only participates in the inflammatory response but also serves a critical role in tumor cells. The present review summarizes the biological functions of the absence or presence of SHARPIN with regard to activating the canonical NF-κB signaling pathway and the effects on p53 and other signaling pathways for the modulation of tumorigenesis. Therefore, this review provides insight into the underlying role and mechanisms of SHARPIN in tumorigenesis, as well as its potential application in cancer therapy.

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“…Data are presented as mean ± standard error of the mean ( SEM ) and significance was assessed by unpaired two‐sided Student's t test and one‐way ANOVA followed by Bonferroni`s post hoc comparisons tests according to Scaglione et al () using GraphPad Prism (RRID:rid_000081). The experimental groups were considered significantly different at * p < .05, ** p < .01, *** p < .001. n represents the number of independent experiments.…”

Section: Methodsmentioning

confidence: 99%

Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination

Göttle

Förster

Gruchot

et al. 2018

Glia

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Remyelination in the adult CNS depends on activation, differentiation, and functional integration of resident oligodendroglial precursor cells (OPCs) and constitutes the only spontaneous neuroregenerative process able to compensate for functional deficits upon loss of oligodendrocytes and myelin sheaths as it is observed in multiple sclerosis. The proteins encoded by p57kip2‐ and by human endogenous retrovirus type W (pHERV‐W) envelope genes were previously identified as negative regulators of OPC maturation. We here focused on the activity of the ENV protein and investigated how it can be neutralized for an improved myelin repair. We could demonstrate that myelination in vitro is severely affected by this protein but that application of an anti‐ENV neutralizing antibody, currently investigated in clinical trials, can rescue the generation of internodes. We then compared p57kip2 and ENV dependent inhibitory mechanisms and found that a dominant negative version of the p57kip2 protein can equally save OPCs from myelination failure in response to ENV‐mediated TLR4 activation. Additional experiments addressing p57kip2's underlying mode of action revealed a direct interaction with ATP6v1d, a central component of a vascular ATPase. Its pharmacological blocking was then shown to exert an analogous myelination rescue effect in presence of the ENV protein. Therefore, our study provides mechanistic insights into oligodendroglial inhibition processes and presents three different means to counteract the anti‐myelination effect of the ENV protein. These observations are therefore of interest in light of understanding the complexity of the numerous oligodendroglial inhibitors and might promote the establishment of novel regenerative therapies.

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PRMT5-mediated regulation of developmental myelination

Cited by 82 publications

References 69 publications

Protein arginine methyltransferase 5 (PRMT5) dysregulation in cancer

Protein arginine methyltransferase 5 (PRMT5) dysregulation in cancer

Shank‑associated RH domain interactor signaling in tumorigenesis (Review)

Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination

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