ArticlePLoS genetics2017
Formation of a TBX20-CASZ1 protein complex is protective against dilated cardiomyopathy and critical for cardiac homeostasis.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Sex-specific response to A1BG loss results in female dilated cardiomyopathy.Biology of sex differences · 2025Article
- Temporal changes in the protein cargo of extracellular vesicles and resultant immune reprogramming after severe burn injury in humans and mice.Frontiers in immunology · 2025Article
- CASZ1 Is Essential for Skin Epidermal Terminal Differentiation.The Journal of investigative dermatology · 2024Article
- CHD4 and SMYD1 repress common transcriptional programs in the developing heart.Development (Cambridge, England) · 2024Article
- Role of the CASZ1 transcription factor in tissue development and disease.European journal of medical research · 2023Review
- Sex Differences in Mouse Cardiac Electrophysiology Revealed by Simultaneous Imaging of Excitation-Contraction Coupling.Journal of cardiovascular development and disease · 2023Article
- The Tbx20-TLE interaction is essential for the maintenance of the second heart field.Development (Cambridge, England) · 2023Article
- Review
- Exome sequencing in multiplex families with left-sided cardiac defects has high yield for disease gene discovery.PLoS genetics · 2022Article
- CHD4 is recruited by GATA4 and NKX2-5 to repress noncardiac gene programs in the developing heart.Genes & development · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation.Developmental cell · 2021Article
- Targeting cardiomyocyte proliferation as a key approach of promoting heart repair after injury.Molecular biomedicine · 2021Review
- Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators.International journal of molecular sciences · 2021Article
- Integrative analysis identifies the association betweenNeurology. Genetics · 2020Article
- Conservation and divergence of protein pathways in the vertebrate heart.PLoS biology · 2019Article
- A novel de novo CASZ1 heterozygous frameshift variant causes dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy.Molecular genetics & genomic medicine · 2019Article
- Proteomic-based approaches to cardiac development and disease.Current opinion in chemical biology · 2019Review
- Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity.Frontiers in immunology · 2018Article
- Proteomic analysis identifies transcriptional cofactors and homeobox transcription factors as TBX18 binding proteins.PloS one · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
By the age of 40, one in five adults without symptoms of cardiovascular disease are at risk for developing congestive heart failure. Within this population, dilated cardiomyopathy (DCM) remains one of the leading causes of disease and death, with nearly half of cases genetically determined. Though genetic and high throughput sequencing-based approaches have identified sporadic and inherited mutations in a multitude of genes implicated in cardiomyopathy, how combinations of asymptomatic mutations lead to cardiac failure remains a mystery. Since a number of studies have implicated mutations of the transcription factor TBX20 in congenital heart diseases, we investigated the underlying mechanisms, using an unbiased systems-based screen to identify novel, cardiac-specific binding partners. We demonstrated that TBX20 physically and genetically interacts with the essential transcription factor CASZ1. This interaction is required for survival, as mice heterozygous for both Tbx20 and Casz1 die post-natally as a result of DCM. A Tbx20 mutation associated with human familial DCM sterically interferes with the TBX20-CASZ1 interaction and provides a physical basis for how this human mutation disrupts normal cardiac function. Finally, we employed quantitative proteomic analyses to define the molecular pathways mis-regulated upon disruption of this novel complex. Collectively, our proteomic, biochemical, genetic, and structural studies suggest that the physical interaction between TBX20 and CASZ1 is required for cardiac homeostasis, and further, that reduction or loss of this critical interaction leads to DCM. This work provides strong evidence that DCM can be inherited through a digenic mechanism.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.