Редактирование: ATF2 (раздел)

==Publications==

{{medline-entry
|title=Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIδ expression in the aged atrium.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29360953
|abstract=c-jun N-terminal kinase (JNK) is a critical stress response kinase that activates in a wide range of physiological and pathological cellular processes. We recently discovered a pivotal role of JNK in the development of atrial arrhythmias in the aged heart, while cardiac CaMKIIδ, another pro-arrhythmic molecule, was also known to enhance atrial arrhythmogenicity. Here, we aimed to reveal a regulatory role of the stress kinase JNK2 isoform on CaMKIIδ expression. Activated JNK2 leads to increased CaMKIIδ protein expression in aged human and mouse atria, evidenced from the reversal of CaMKIIδ up-regulation in JNK2 inhibitor treated wild-type aged mice. This JNK2 action in CaMKIIδ expression was further confirmed in HL-1 myocytes co-infected with AdMKK7D-JNK2, but not when co-infected with AdMKK7D-JNK1. JNK2-specific inhibition (either by a JNK2 inhibitor or overexpression of inactivated dominant-negative JNK2 (JNK2dn) completely attenuated JNK activator anisomycin-induced CaMKIIδ up-regulation in HL-1 myocytes, whereas overexpression of JNK1dn did not. Moreover, up-regulated CaMKIIδ mRNA along with substantially increased phosphorylation of JNK downstream transcription factor c-jun [but not activating transcription factor2 ([[ATF2]])] were exhibited in both aged atria (humans and mice) and transiently JNK activated HL-1 myocytes. Cross-linked chromatin-immunoprecipitation assays (XChIP) revealed that both c-jun and [[ATF2]] were bound to the CaMKIIδ promoter, but significantly increased binding of c-jun only occurred in the presence of anisomycin and JNK inhibition alleviated this anisomycin-elevated c-jun binding. Mutated CaMKII consensus c-jun binding sites impaired its promoter activity. Enhanced transcriptional activity of CaMKIIδ by anisomycin was also completely reversed to the baseline by either JNK2 siRNA or c-jun siRNA knockdown. JNK2 activation up-regulates CaMKIIδ expression in the aged atrium. This JNK2 regulation in CaMKIIδ expression occurs at the transcription level through the JNK downstream transcription factor c-jun. The discovery of this novel molecular mechanism of JNK2-regulated CaMKII expression sheds new light on possible anti-arrhythmia drug development.
|mesh-terms=* Adult
* Age Factors
* Aged
* Aging
* Animals
* Arrhythmias, Cardiac
* Binding Sites
* Calcium-Calmodulin-Dependent Protein Kinase Type 2
* Cell Line
* Enzyme Activation
* Female
* Gene Expression Regulation, Enzymologic
* Heart Atria
* Humans
* Male
* Mice, Inbred C57BL
* Mice, Transgenic
* Middle Aged
* Mitogen-Activated Protein Kinase 9
* Myocytes, Cardiac
* Phosphorylation
* Promoter Regions, Genetic
* Proto-Oncogene Proteins c-jun
* Transcription, Genetic
* Transcriptional Activation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915954
}}
{{medline-entry
|title=Prmt7 Deficiency Causes Reduced Skeletal Muscle Oxidative Metabolism and Age-Related Obesity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27207521
|abstract=Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling-transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity. Prmt7(-/-) muscles exhibit decreased oxidative metabolism with decreased expression of genes involved in muscle oxidative metabolism, including [[PGC]]-1α. Consistently, Prmt7(-/-) mice exhibited significantly reduced endurance exercise capacities. Furthermore, Prmt7(-/-) mice exhibit decreased energy expenditure, which might contribute to the exacerbated age-related obesity of Prmt7(-/-) mice. Similarly to Prmt7(-/-) muscles, Prmt7 depletion in myoblasts also reduces [[PGC]]-1α expression and [[PGC]]-1α-promoter driven reporter activities. Prmt7 regulates [[PGC]]-1α expression through interaction with and activation of p38 mitogen-activated protein kinase (p38MAPK), which in turn activates [[ATF2]], an upstream transcriptional activator for [[PGC]]-1α. Taken together, Prmt7 is a novel regulator for muscle oxidative metabolism via activation of p38MAPK/[[ATF2]]/[[PGC]]-1α.
|mesh-terms=* Activating Transcription Factor 2
* Aging
* Animals
* Energy Metabolism
* Female
* Lipids
* Male
* Mice
* Mice, Knockout
* Muscle, Skeletal
* Myoblasts
* Obesity
* Oxygen Consumption
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Physical Conditioning, Animal
* Physical Endurance
* Promoter Regions, Genetic
* Protein-Arginine N-Methyltransferases
* Signal Transduction

|full-text-url=https://sci-hub.do/10.2337/db15-1500
}}