ArticleScientific reports2021
E3-ligase knock down revealed differential titin degradation by autopagy and the ubiquitin proteasome system.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch.eLife · 2026Article
- Mechanotransduction Failure and Molecular Rescue in Gastric Cancer: Kinetotherapy Across the IL-6/STAT3-Myostatin/ACVR2B-Akt/mTOR Axis.Medical sciences (Basel, Switzerland) · 2026Review
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- Exploring Novel E3 Ligases and Neosubstrates for Molecular Glue Degraders and Therapeutic Applications in Cancer.Oncology research · 2026Review
- MyoMed205 Counteracts Titin Hyperphosphorylation and the Expression of Contraction-Regulating Proteins in a Rat Model of HFpEF.Journal of cachexia, sarcopenia and muscle · 2025Article
- HCM-Associated MuRF1 Variants Compromise Ubiquitylation and Are Predicted to Alter Protein Structure.International journal of molecular sciences · 2025Article
- Modulation of Titin and Contraction-Regulating Proteins in a Rat Model of Heart Failure with Preserved Ejection Fraction: Limb vs. Diaphragmatic Muscle.International journal of molecular sciences · 2024Article
- Uncovering the mechanisms of MuRF1-induced ubiquitylation and revealing similarities with MuRF2 and MuRF3.Biochemistry and biophysics reports · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Integrative multi-omics summary-based mendelian randomization identifies key oxidative stress-related genes as therapeutic targets for atrial fibrillation and flutter.Frontiers in genetics · 2024Article
- RING Finger Protein 10 Regulates AP-1/Meox2 to Mediate Pirarubicin-Induced Cardiomyocyte Apoptosis.Oxidative medicine and cellular longevity · 2023Article
- Oxygen-dependent regulation of E3(SCF)ubiquitin ligases and a Skp1-associated JmjD6 homolog in development of the social amoeba Dictyostelium.The Journal of biological chemistry · 2022Article
- Disulfiram Oxy-Derivatives Suppress Protein Retrotranslocation across the ER Membrane to the Cytosol and Initiate Paraptosis-like Cell Death.Membranes · 2022Article
- Protein Quality Control at the Sarcomere: Titin Protection and Turnover and Implications for Disease Development.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The sarcomere protein titin is a major determinant of cardiomyocyte stiffness and ventricular distensibility. The constant mechanical stress on titin requires well-controlled protein quality control, the exact mechanisms of which have not yet been fully elucidated. Here, we analyzed E3-ligases potentially responsible for cardiac titin ubiquitination and specifically studied the involvement of the autophagosomal system in titin degradation. Pharmacological inhibition of autophagy and the proteasome in cultured primary rat cardiomyocytes significantly elevated titin ubiquitination and increased titin degradation. Using in-vitro pull down assays we identified binding of E3-ligases MuRF1-3, CHIP and Fbx32 to several titin domains. Immunofluorescence analysis showed sarcomeric localization of the E3-ligases. siRNA-mediated knock-down of the E3-ligases MuRF-1, -3 and a combination of CHIP/Fbx32 significantly reduced autophagy-related titin ubiquitination, whereas knock-down of MuRF-2 and -3 reduced proteasome-related titin ubiquitination. We demonstrated that the proteasomal and the autophagosomal-lysosomal system participate in degradation of the titin filament. We found that ubiquitination and degradation of titin are partially regulated by E3-ligases of the MuRF family. We further identified CHIP and Fbx32 as E3-ligases involved in titin ubiquitination.
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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.