Structure, Activity and Function of the Protein Arginine Methyltransferase 6

Gupta, Somlee; Kadumuri, Rajashekar Varma; Singh, Anjali Kumari; Chavali, Sreenivas; Dhayalan, Arunkumar

doi:10.3390/life11090951

“…PRMT6, a type I PRMT, di-methylates the arginine residues of both histones and non-histones asymmetrically [16]. Numerous pieces of evidence suggest that PRMT6 is involved in a variety of cellular functions, including cellular division, RNA metabolism, cellular senescence, and cellular homeostasis [17]. Now, it is widely reported that PRMT6 acts as a tumor mediator and exerts a dual role in human cancer.…”

Section: Introductionmentioning

confidence: 99%

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B

Wang

¹

,

Xiao

²

,

Wu

³

et al. 2023

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PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.

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“…Emerging evidence indicates that other PTMs, particularly methylation and the adding of poly (ADP-ribose) (PAR) chains (PARylation), influence FOXO3a activity. In mice, the stimulation of PRMT6 (protein arginine methyltransferase 6) has been found to promote the methylation of FOXO3a at Arg188 and Arg249, resulting in enhanced autophagy activity [ 77 , 78 ]. On the other hand, the PTM regulated by poly (ADP-ribose) polymerase-1 (PARP1) may be triggered by ROS and is implicated in the control of FOXO3a activity.…”

Section: Regulation Of Foxo3a Upon Oxidative Stressmentioning

confidence: 99%

Role of FOXO3a Transcription Factor in the Regulation of Liver Oxidative Injury

Jin

¹

,

Zhang

²

,

He

³

et al. 2022

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Oxidative stress has been identified as a key mechanism in liver damage caused by various chemicals. The transcription factor FOXO3a has emerged as a critical regulator of redox imbalance. Multiple post-translational changes and epigenetic processes closely regulate the activity of FOXO3a, resulting in synergistic or competing impacts on its subcellular localization, stability, protein–protein interactions, DNA binding affinity, and transcriptional programs. Depending on the chemical nature and subcellular context, the oxidative-stress-mediated activation of FOXO3a can induce multiple transcriptional programs that play crucial roles in oxidative injury to the liver by chemicals. Here, we mainly review the role of FOXO3a in coordinating programs of genes that are essential for cellular homeostasis, with an emphasis on exploring the regulatory mechanisms and potential application of FOXO3a as a therapeutic target to prevent and treat liver oxidative injury.

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“…PRMT6, a type I PRMT, dimethylates the arginine residues of both histones and non-histones asymmetrically [16]. Numerous pieces of evidence suggest that PRMT6 is involved in a variety of cellular functions, including cellular division, RNA metabolism, cellular senescence, and cellular homeostasis [17]. Now, it is widely reported that PRMT6 acts as a tumor mediator and exerts a dual role in human cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Now, it is widely reported that PRMT6 acts as a tumor mediator and exerts a dual role in human cancer. In hepatocellular carcinoma, there is a signi cant correlation between decreased PRMT6 expression and short overall survival, whereas PRMT6 overexpression is associated with tumorigenicity and invasiveness in gastric cancer and lung cancer [17,18]. It has been described as an arginine methyltransferase that methylates CRAF, P16, and BAG5 proteins involved in tumor progression [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B

Wang¹,

Wang²,

Xiao³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

PRMT6, a type I arginine methyltransferase, di-methylates the arginine residues of both histones and non-histones asymmetrically. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Here, we aim to uncover the essential role and underlying mechanisms of PRMT6 in promoting glioblastoma (GBM) proliferation. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results. Further, we found that PRMT6 attenuates the protein stability of CDKN1B by promoting its degradation. Subsequent mechanistic investigations showed that PRMT6 maintains the transcription of CDC20 by activating histone methylation mark (H3R2me2a), and CDC20 interacts with and destabilizes CDKN1B. Rescue experimental results confirmed that PRMT6 promotes the ubiquitinated degradation of CDKN1B and cell proliferation via CDC20. We also verified that the PRMT6 inhibitor (EPZ020411) could attenuate the proliferative effect of GBM cells. Our findings illustrate that PRMT6, an epigenetic mediator, promotes CDC20 transcription via H3R2me2a to mediate the degradation of CDKN1B to facilitate GBM progression. Targeting PRMT6-CDC20-CDKN1B axis might be a promising therapeutic strategy for GBM.

show abstract

Structure, Activity and Function of the Protein Arginine Methyltransferase 6

Cited by 19 publications

References 195 publications

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B

Role of FOXO3a Transcription Factor in the Regulation of Liver Oxidative Injury

PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B

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