ArticlePloS one2016
IBMPFD Disease-Causing Mutant VCP/p97 Proteins Are Targets of Autophagic-Lysosomal Degradation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- The Autophagic Interaction Between p97/VCP and ABP Protein Expressions in Sertoli Cell Line: the Effects of Chloroquine and Rapamycin.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Induced-proximity therapeutics for targeted protein and RNA degradation: An organic chemistry Perspective-A review.Current research in structural biology · 2026Review
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes.International journal of molecular sciences · 2024Review
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Novel Variants in theGenes · 2023Article
- Skeletal muscle cell protein dysregulation highlights the pathogenesis mechanism of myopathy-associated p97/VCP R155H mutations.Frontiers in neurology · 2023Article
- Novel protein complexes containing autophagy and UPS components regulate proteasome-dependent PARK2 recruitment onto mitochondria and PARK2-PARK6 activity during mitophagy.Cell death & disease · 2022Article
- FYCO1 Increase and Effect of Arimoclomol-Treatment in HumanBiomedicines · 2022Article
- Pathogenic variants of Valosin-containing protein induce lysosomal damage and transcriptional activation of autophagy regulators in neuronal cells.Neuropathology and applied neurobiology · 2022Article
- A clinicopathologic study of malignancy in VCP-associated multisystem proteinopathy.Orphanet journal of rare diseases · 2022Article
- A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress.Scientific reports · 2022Article
- Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy.International journal of molecular sciences · 2022Review
- Autophagy and Hepatic Tumor Microenvironment Associated Dormancy.Journal of gastrointestinal cancer · 2021Review
- CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression.Autophagy · 2021Article
- Disruption of p97/VCP induces autophagosome accumulation, cell cycle arrest and apoptosis in human choriocarcinoma cells.Molecular biology reports · 2021Article
- Crosstalk between autophagy and DNA repair systems.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Parkin Coordinates Platelet Stress Response in Diabetes Mellitus: A Big Role in a Small Cell.International journal of molecular sciences · 2020Article
- Valosin-Containing Protein, a Calcium-Associated ATPase Protein, in Endoplasmic Reticulum and Mitochondrial Function and Its Implications for Diseases.International journal of molecular sciences · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone. We showed that, unlike commonly studied R155C or R191Q mutants, the P137L mutant protein stimulated both autophagosome and autolysosome formation. Moreover, P137L mutant protein itself was a substrate of autophagy. Starvation- and mTOR inhibition-induced autophagy led to the degradation of the P137L mutant protein, while preserving the wild-type and functional VCP/p97. Strikingly, similar to the P137L mutant, other IBMPFD-related VCP/p97 mutants, namely R93C and G157R mutants induced autophagosome and autolysosome formation; and G157R mutant formed aggregates that could be cleared by autophagy. Therefore, cellular phenotypes caused by P137L mutant expression were not isolated observations, and some other IBMPFD disease-related VCP/p97 mutations could lead to similar outcomes. Our results indicate that cellular mechanisms leading to IBMPFD disease may be various, and underline the importance of studying different disease-associated mutations in order to better understand human pathologies and tailor mutation-specific treatment strategies.
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