Trim63 Reference Search Result - Rat Genome Database

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RGD ID	Title	Citation	Abstract	PubMed	Pub Date
11070159	Does p.Q247X in TRIM63 cause human hypertrophic cardiomyopathy?	Ploski R, etal., Circ Res. 2014 Jan 17;114(2):e2-5. doi: 10.1161/CIRCRESAHA.114.302662.	RATIONALE: Variants in TRIM63, including a nonsense mutation (p.Q247X), have been suggested recently to cause hypertrophic cardiomyopathy. OBJECTIVE: To verify pathogenicity of TRIM63 p.Q247X detected by whole-exome sequenci ... (more) ng in a symptomless professional sports player seeking medical advice because of a prolonged QT interval found during a routine check-up. METHODS AND RESULTS: Clinical studies were performed in the proband and his mother, who also carried TRIM63 p.Q247X. No evidence of hypertrophic cardiomyopathy was found in either person. CONCLUSIONS: The p.Q247X variant in TRIM63 is not likely to be a highly penetrant variant causing hypertrophic cardiomyopathy.	24436435	2014-04-01
11064971	Human molecular genetic and functional studies identify TRIM63, encoding Muscle RING Finger Protein 1, as a novel gene for human hypertrophic cardiomyopathy.	Chen SN, etal., Circ Res. 2012 Sep 14;111(7):907-19. doi: 10.1161/CIRCRESAHA.112.270207. Epub 2012 Jul 19.	RATIONALE: A delicate balance between protein synthesis and degradation maintains cardiac size and function. TRIM63 encoding Muscle RING Finger 1 (MuRF1) maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degrada ... (more) tion by the ubiquitin-proteasome system (UPS). OBJECTIVE: To determine the pathogenic role of TRIM63 in human hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Sequencing of TRIM63 gene in 302 HCM probands (250 white individuals) and 339 control subjects (262 white individuals) led to identification of 2 missense (p.A48V and p.I130M) and a deletion (p.Q247*) variants exclusively in the HCM probands. These 3 variants were absent in 751 additional control subjects screened by TaqMan assays. Likewise, rare variants were enriched in the white HCM population (11/250, 4.4% versus 3/262, 1.1%, respectively, P=0.024). Expression of the mutant TRIM63 was associated with mislocalization of TRIM63 to sarcomere Z disks, impaired auto-ubiquitination, reduced ubiquitination and UPS-mediated degradation of myosin heavy chain 6, cardiac myosin binding protein C, calcineurin (PPP3CB), and p-MTOR in adult cardiac myocytes. Induced expression of the mutant TRIM63 in the mouse heart was associated with cardiac hypertrophy, activation of the MTOR-S6K and calcineurin pathways, and expression of the hypertrophic markers, which were normalized on turning off expression of the mutant protein. CONCLUSIONS: TRIM63 mutations, identified in patients with HCM, impart loss-of-function effects on E3 ligase activity and are probably causal mutations in HCM. The findings implicate impaired protein degradation in the pathogenesis of HCM.	22821932	2012-04-01
11564426	Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63.	von Grabowiecki Y, etal., Elife. 2016 Feb 26;5. pii: e10528. doi: 10.7554/eLife.10528.	Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common deno ... (more) minator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice. In particular, we observed increased p63 protein levels in the fibers of atrophic muscles via denervation-dependent and -independent mechanisms. At a functional level, we demonstrated that TAp63 and p53 transactivate the promoter and increased the expression of Trim63 (MuRF1), an effector of muscle atrophy. Altogether, these results suggest a novel function for p63 as a contributor to muscular atrophic processes via the regulation of multiple genes, including the muscle atrophy gene Trim63.	26919175	2016-11-01