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PubMed:15769446 JSONTXT

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DisGeNET

Id Subject Object Predicate Lexical cue
T0 151-158 gene:5555 denotes cMyBP-C
T1 183-219 disease:C0949658 denotes familial hypertrophic cardiomyopathy
T2 151-158 gene:5554 denotes cMyBP-C
T3 183-219 disease:C0949658 denotes familial hypertrophic cardiomyopathy
T4 151-158 gene:5555 denotes cMyBP-C
T5 221-224 disease:C0745103 denotes FHC
T6 151-158 gene:5554 denotes cMyBP-C
T7 221-224 disease:C0745103 denotes FHC
R1 T0 T1 associated_with cMyBP-C,familial hypertrophic cardiomyopathy
R2 T2 T3 associated_with cMyBP-C,familial hypertrophic cardiomyopathy
R3 T4 T5 associated_with cMyBP-C,FHC
R4 T6 T7 associated_with cMyBP-C,FHC

DisGeNET5_gene_disease

Id Subject Object Predicate Lexical cue
15769446-1#39#46#gene5554 151-158 gene5554 denotes cMyBP-C
15769446-1#39#46#gene5555 151-158 gene5555 denotes cMyBP-C
15769446-1#39#46#gene5554 151-158 gene5554 denotes cMyBP-C
15769446-1#39#46#gene5555 151-158 gene5555 denotes cMyBP-C
15769446-1#71#107#diseaseC0949658 183-219 diseaseC0949658 denotes familial hypertrophic cardiomyopathy
15769446-1#109#112#diseaseC0745103 221-224 diseaseC0745103 denotes FHC
39#46#gene555471#107#diseaseC0949658 15769446-1#39#46#gene5554 15769446-1#71#107#diseaseC0949658 associated_with cMyBP-C,familial hypertrophic cardiomyopathy
39#46#gene5554109#112#diseaseC0745103 15769446-1#39#46#gene5554 15769446-1#109#112#diseaseC0745103 associated_with cMyBP-C,FHC
39#46#gene555571#107#diseaseC0949658 15769446-1#39#46#gene5555 15769446-1#71#107#diseaseC0949658 associated_with cMyBP-C,familial hypertrophic cardiomyopathy
39#46#gene5555109#112#diseaseC0745103 15769446-1#39#46#gene5555 15769446-1#109#112#diseaseC0745103 associated_with cMyBP-C,FHC
39#46#gene555471#107#diseaseC0949658 15769446-1#39#46#gene5554 15769446-1#71#107#diseaseC0949658 associated_with cMyBP-C,familial hypertrophic cardiomyopathy
39#46#gene5554109#112#diseaseC0745103 15769446-1#39#46#gene5554 15769446-1#109#112#diseaseC0745103 associated_with cMyBP-C,FHC
39#46#gene555571#107#diseaseC0949658 15769446-1#39#46#gene5555 15769446-1#71#107#diseaseC0949658 associated_with cMyBP-C,familial hypertrophic cardiomyopathy
39#46#gene5555109#112#diseaseC0745103 15769446-1#39#46#gene5555 15769446-1#109#112#diseaseC0745103 associated_with cMyBP-C,FHC

PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 112-508 OBJECTIVE denotes Most cardiac myosin binding protein C (cMyBP-C) gene mutations causing familial hypertrophic cardiomyopathy (FHC) result in C-terminal truncated proteins. However, truncated cMyBP-Cs were undetectable in myocardial tissue of FHC patients. In the present study, we investigated whether truncated cMyBP-Cs are subject to accelerated degradation by the lysosome or ubiquitin-proteasome system (UPS).
T2 530-1383 RESULTS denotes By using an adenovirus-based approach, we analyzed expression and localization of myc-tagged truncated proteins (M6t 3%, M7t 80% truncation, both mutations have been identified in FHC patients) compared to wild type (WT) in neonatal rat cardiomyocytes. Despite similar mRNA levels, protein expression of M6t and M7t was markedly lower than WT (70+/-4% and 11+/-5% of WT, respectively, p<0.05). M6t exhibited weak incorporation in the sarcomere, whereas M7t was mis-incorporated at the Z-disk and formed ubiquitin-positive aggregates. The lysosome inhibitor bafilomycin only slightly raised the protein level of M7t, whereas the UPS inhibitors lactacystin or MG132 markedly raised M6t and M7t to WT level. Using an adenovirus encoding a fluorescent reporter of UPS activity, we demonstrate that mutant cMyBP-Cs impair the proteolytic capacity of the UPS.
T3 1396-1726 CONCLUSIONS denotes Truncated cMyBP-Cs are preferentially degraded by the UPS, which, in turn, may competitively inhibit breakdown of other UPS substrates. Since the UPS plays an important role in a variety of fundamental cellular processes, we propose impairment of this system by mutant cMyBP-Cs as a contributing factor to the pathogenesis of FHC.