Редактирование: CARM1

Histone-arginine methyltransferase CARM1 (EC 2.1.1.319) (Coactivator-associated arginine methyltransferase 1) (Protein arginine N-methyltransferase 4) [PRMT4]

==Publications==

{{medline-entry
|title=[[CARM1]] regulates senescence during airway epithelial cell injury in COPD pathogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31461302
|abstract=Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease. Although cigarette smoke was considered the main cause of development, the heterogeneous nature of the disease leaves it unclear whether other factors contribute to the predisposition or impaired regeneration response observed. Recently, epigenetic modification has emerged to be a key player in the pathogenesis of COPD. The addition of methyl groups to arginine residues in both histone and nonhistone proteins by protein arginine methyltransferases (PRMTs) is an important posttranslational epigenetic modification event regulating cellular proliferation, differentiation, apoptosis, and senescence. Here, we hypothesize that coactivator-associated arginine methyltransferase-1 ([[CARM1]]) regulates airway epithelial cell injury in COPD pathogenesis by controlling cellular senescence. Using the naphthalene (NA)-induced mouse model of airway epithelial damage, we demonstrate that loss of CC10-positive club cells is accompanied by a reduction in [[CARM1]]-expressing cells of the airway epithelium. Furthermore, [i]Carm1[/i] haploinsuffficent mice showed perturbed club cell regeneration following NA treatment. In addition, [[CARM1]] reduction led to decreased numbers of antisenescent sirtuin 1-expressing cells accompanied by higher p21, p16, and β-galactosidase-positive senescent cells in the mouse airway following NA treatment. Importantly, [[CARM1]]-silenced human bronchial epithelial cells showed impaired wound healing and higher β-galactosidase activity. These results demonstrate that [[CARM1]] contributes to airway repair and regeneration by regulating airway epithelial cell senescence.
|mesh-terms=* Aged
* Animals
* Apoptosis
* Cell Differentiation
* Cell Proliferation
* Cellular Senescence
* Epithelial Cells
* Female
* Humans
* Male
* Mice, Inbred C57BL
* Mice, Knockout
* Middle Aged
* Naphthalenes
* Protein-Arginine N-Methyltransferases
* Pulmonary Disease, Chronic Obstructive
* Respiratory Mucosa
* Wound Healing
|keywords=* CARM1
* COPD
* airway epithelium
* senescence
|full-text-url=https://sci-hub.do/10.1152/ajplung.00441.2018
}}
{{medline-entry
|title=Nuclear AMPK regulated [[CARM1]] stabilization impacts autophagy in aged heart.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28315332
|abstract=Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 ([[CARM1]]) participates in many cellular processes, including autophagy in mammals. However, the effect of [[CARM1]] in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and [[CARM1]] in aging heart. We found that fasting could promote autophagy in young hearts but not in aged hearts. The [[CARM1]] stabilization is markedly decrease in aged hearts, which impaired nucleus [[TFEB]]-[[CARM1]] complex and autophagy flux. Further, S-phase kinase-associated protein 2([[SKP2]]), responsible for [[CARM1]] degradation, was increased in aged hearts. We further validated that AMPK dependent FoxO3 phosphorylation was markedly reduced in nucleus, the decreased nuclear AMPK-FoxO3 activity fails to suppress [[SKP2]]-E3 ubiquitin ligase. This loss of repression leads to The [[CARM1]] level and autophagy in aged hearts could be restored through AMPK activation. Taken together, AMPK deficiency results in nuclear [[CARM1]] decrease mediated in part by [[SKP2]], contributing to autophagy dysfunction in aged hearts. Our results identified nuclear AMPK controlled [[CARM1]] stabilization as a new actor that regulates cardiac autophagy.
|mesh-terms=* AMP-Activated Protein Kinases
* Aging
* Animals
* Animals, Newborn
* Autophagy
* Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
* Cell Nucleus
* Fasting
* Forkhead Box Protein O3
* Gene Expression Regulation
* Male
* Mice
* Mice, Inbred C57BL
* Myocardium
* Myocytes, Cardiac
* Phosphorylation
* Primary Cell Culture
* Protein Stability
* Protein-Arginine N-Methyltransferases
* Proteolysis
* S-Phase Kinase-Associated Proteins
* Signal Transduction
* Ubiquitin-Protein Ligases
|keywords=* AMP-Activated protein kinase
* Aging
* Autophagy
* Coactivator-associated arginine methyltransferase 1
* SKP2containing SCF (SKP1-cullin1-F-box protein) E3 ubiquitin ligase
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2017.03.053
}}
{{medline-entry
|title=Coactivator-Associated Arginine Methyltransferase-1 Function in Alveolar Epithelial Senescence and Elastase-Induced Emphysema Susceptibility.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25906418
|abstract=Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases worldwide. A major feature of COPD is emphysema, which is the progressive loss of alveolar tissue. Coactivator-associated arginine methyltransferase-1 ([[CARM1]]) regulates histone methylation and the transcription of genes involved in senescence, proliferation, and differentiation. Complete loss of [[CARM1]] leads to disrupted differentiation and maturation of alveolar epithelial type II (ATII) cells. We thus hypothesized that [[CARM1]] regulates the development and progression of emphysema. To address this, we investigated the contribution of [[CARM1]] to alveolar rarefication using the mouse model of elastase-induced emphysema in vivo and small interfering (si)RNA-mediated knockdown in ATII-like LA4 cells in vitro. We demonstrate that emphysema progression in vivo is associated with a time-dependent down-regulation of [[CARM1]]. Importantly, elastase-treated [[CARM1]] haploinsufficient mice show significantly increased airspace enlargement (52.5 ± 9.6 μm versus 38.8 ± 5.5 μm; P < 0.01) and lung compliance (2.8 ± 0.32 μl/cm H2O versus 2.4 ± 0.4 μl/cm H2O; P < 0.04) compared with controls. The knockdown of [[CARM1]] in LA4 cells led to decreased sirtuin 1 expression (0.034 ± 0.003 versus 0.022 ± 0.001; P < 0.05) but increased expression of p16 (0.27 ± 0.013 versus 0.31 ± 0.010; P < 0.5) and p21 (0.81 ± 0.088 versus 1.28 ± 0.063; P < 0.01) and higher β-galactosidase-positive senescent cells (50.57 ± 7.36% versus 2.21 ± 0.34%; P < 0.001) compared with scrambled siRNA. We further demonstrated that [[CARM1]] haploinsufficiency impairs transdifferentiation and wound healing (32.18 ± 0.9512% versus 8.769 ± 1.967%; P < 0.001) of alveolar epithelial cells. Overall, these results reveal a novel function of [[CARM1]] in regulating emphysema development and premature lung aging via alveolar senescence as well as impaired regeneration, repair, and differentiation of ATII cells. 
|mesh-terms=* Alveolar Epithelial Cells
* Animals
* Cell Differentiation
* Cell Line
* Cellular Senescence
* Female
* Genetic Predisposition to Disease
* Haploinsufficiency
* Mice, Inbred C57BL
* Pancreatic Elastase
* Protein-Arginine N-Methyltransferases
* Pulmonary Emphysema
|keywords=* alveolar type II cells
* coactivator-associated arginine methyltransferase 1
* elastase-treatment
* emphysema
* lung regeneration
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455466
}}