Why the study?
Due to the roles of BAG3 in cardiomyopathies and the complexity of BAG3-protein interactions, understanding these interactions in cardiomyocytes was needed.
This proteomic and transcriptomic study identifies 387 BAG3-interacting proteins across key cardiomyopathy-enriched gene sets, elucidating molecular mechanisms behind both the cardioprotective and potentially adverse effects of BAG3 in heart failure.
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In vitro BAG3 interactome data warrant caution before clinical translation; leaves open relevance to human cardiomyopathies pending in vivo validation.
gene result in cardiomyopathies. Due to its roles in cardiomyopathies and the complexity of BAG3-protein interactions, it is important to understand these protein interactions given the importance of the multifunctional cochaperone BAG3 in cardiomyocytes, using an in vitro cardiomyocyte model. The experimental assay was conducted using high pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the human AC16 cardiomyocyte cell line with BioID technology. Proteins with BAG3-interaction were identified in all the 28 hallmark gene sets enriched in idiopathic cardiomyopathies and/or ischemic disease. Among the 24 hallmark gene sets enriched in both idiopathic cardiomyopathies and ischemic disease, 15 gene sets had at least 3 proteins with BAG3-interaction. This study highlights BAG3 protein interactions, unveiling the key gene sets affected in cardiomyopathies, which help to explain the molecular mechanisms of the cardioprotective effects of BAG3. In addition, this study also highlighted the complexity of proteins with BAG3 interactions, implying unwanted effects of BAG3.
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Qu et al. (2024) studied this question.
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