Cardiomyopathy Is Associated with Ribosomal Protein Gene Haplo-Insufficiency in<i>Drosophila melanogaster</i>

Casad, Michelle; Abraham, Dennis; Kim, Il-man; Frangakis, Stephan; Dong, Brian; Lin, Na; Wolf, Matthew J.; Rockman, Howard A.

doi:10.1534/genetics.111.131482

Cited by 27 publications

(24 citation statements)

References 53 publications

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“…Several RPs have been implicated in the development and progression of cardiovascular diseases . For instance, the Minute syndrome in Drosophila , which is associated with RP haploinsufficiency, also affects the heart . The cardiomyopathy associated with the Minute syndrome is caused by haploinsufficiency for genes encoding cytoplasmic RPs.…”

Section: Ribosomal Proteins and The Pathogenesis Of Human Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications

Wang

Nag

Zhang

et al. 2014

Medicinal Research Reviews

184

154

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Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins (RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs-MDM2 interactions, resulting in p53-dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53-independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.

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Section: Ribosomal Proteins and The Pathogenesis Of Human Diseasesmentioning

confidence: 99%

“…The cardiomyopathy associated with the Minute syndrome is caused by haploinsufficiency for genes encoding cytoplasmic RPs. Specifically, the heart‐specific knockdown of S15a severely impairs the cardiac function in adult Drosophila . RPs also have a role in the vascular system.…”

Section: Ribosomal Proteins and The Pathogenesis Of Human Diseasesmentioning

confidence: 99%

Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications

Wang

Nag

Zhang

et al. 2014

Medicinal Research Reviews

184

154

View full text Add to dashboard Cite

show abstract

“…The Drosophila heart is sensitive to alterations in structural and contractile proteins that can alter contractility (Wolf et al 2006; Allikian et al 2007; Taghli-Lamallem et al 2008), as well as signaling in pathways such as Notch, Rhomboid 3, SMAD, and insulin and ribosomal functions can change heart function in flies (Goldstein et al 2011; Yu et al 2010; Kim et al 2010; Wessells et al 2004; Casad et al 2011). Large scale RNAi screening and proteomics studies have also identified complexes important for Drosophila heart function (Neely et al 2010; Cammarato et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy

Casad

Daniels

et al. 2012

Mol Genet Genomics

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Drosophila is a useful model organism in which to study the genetics of human diseases, including recent advances in identification of the genetics of heart development and disease in the fly. To identify novel genes that cause cardiomyopathy, we performed a deficiency screen in adult Drosophila. Using optical coherence tomography to phenotype cardiac function in awake adult Drosophila, we identified Df(1)Exel6240 as having cardiomyopathy. Using a number of strategies including customized smaller deletions, screening of mutant alleles, and transgenic rescue, we identified CG3226 as the causative gene for this deficiency. CG3226 is an uncharacterized gene in Drosophila possessing homology to the mammalian Siah-interacting-protein (SIP) gene. Mammalian SIP functions as an adaptor protein involved in one of the β-catenin degradation complexes. To investigate the effects of altering β-catenin/Armadillo signaling in the adult fly, we measured heart function in flies expressing either constitutively active Armadillo or transgenic constructs that block Armadillo signaling, specifically in the heart. While increasing Armadillo signaling in the heart did not have an effect on adult heart function, decreasing Armadillo signaling in the fly heart caused the significant reduction in heart chamber size. In summary, we show that deletion of CG3226, which has homology to mammalian SIP, causes cardiomyopathy in adult Drosophila. Alterations in Armadillo signaling during development lead to important changes in the size and function of the adult heart.

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“…Several r-proteins were identified as causative factors of various CVDs, including r-protein Rps15, implicated in the progression of cardiomyopathy [145], and Rpl17, malfunctions of which have been linked to the development of carotid atherosclerotic vascular disease [146]. What makes these r-proteins pro-pathogenic remains unanswered.…”

Section: Ribosomementioning

confidence: 99%

Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases

Ghosh

Shcherbik

2020

IJMS

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Cardiovascular diseases (CVDs) are a group of disorders that affect the heart and blood vessels. Due to their multifactorial nature and wide variation, CVDs are the leading cause of death worldwide. Understanding the molecular alterations leading to the development of heart and vessel pathologies is crucial for successfully treating and preventing CVDs. One of the causative factors of CVD etiology and progression is acute oxidative stress, a toxic condition characterized by elevated intracellular levels of reactive oxygen species (ROS). Left unabated, ROS can damage virtually any cellular component and affect essential biological processes, including protein synthesis. Defective or insufficient protein translation results in production of faulty protein products and disturbances of protein homeostasis, thus promoting pathologies. The relationships between translational dysregulation, ROS, and cardiovascular disorders will be examined in this review.

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Cardiomyopathy Is Associated with Ribosomal Protein Gene Haplo-Insufficiency inDrosophila melanogaster

Cited by 27 publications

References 53 publications

Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications

Ribosomal Proteins and Human Diseases: Pathogenesis, Molecular Mechanisms, and Therapeutic Implications

Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy

Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases

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