ArticleHuman molecular genetics2008
Loss of polycystin-1 causes centrosome amplification and genomic instability.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 93 citations in OpenAlex.
- Genome-Based Advances in Modeling Renal Ciliopathies and Enhancing Patient Care.Kidney & blood pressure research · 2025Review
- Bystanders or active players: the role of extra centrosomes as signaling hubs.Cancer metastasis reviews · 2024Review
- Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Amplified centrosomes-more than just a threat.EMBO reports · 2024Review
- Reduced decay-accelerating factor expression promotes complement-mediated cystogenesis in murine ADPKD.JCI insight · 2024Article
- Overexpression of SMYD3 Promotes Autosomal Dominant Polycystic Kidney Disease by Mediating Cell Proliferation and Genome Instability.Biomedicines · 2024Article
- Inhibiting centrosome clustering reduces cystogenesis and improves kidney function in autosomal dominant polycystic kidney disease.JCI insight · 2024Article
- Racgap1 knockdown results in cells with multiple cilia due to cytokinesis failure.Annals of human genetics · 2024Article
- Folate conjugated nanomedicines for selective inhibition of mTOR signaling in polycystic kidneys at clinically relevant doses.Biomaterials · 2023Article
- Polycystin-1 Interacting Protein-1 (CU062) Interacts with the Ectodomain of Polycystin-1 (PC1).Cells · 2023Article
- Computational study of biomechanical drivers of renal cystogenesis.Biomechanics and modeling in mechanobiology · 2023Article
- Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development.Kidney international · 2023Article
- Wildtype heterogeneity contributes to clonal variability in genome edited cells.Scientific reports · 2022Article
- Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Antioxidant enzyme peroxiredoxin 5 regulates cyst growth and ciliogenesis via modulating Plk1 stability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Role of DNA-Dependent Protein Kinase in Mediating Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.International journal of molecular sciences · 2021Article
- Epithelial proliferation and cell cycle dysregulation in kidney injury and disease.Kidney international · 2021Review
- Article
- Loss of polycystins suppresses deciliation via the activation of the centrosomal integrity pathway.Life science alliance · 2020Article
- Rapamycin treatment correlates changes in primary cilia expression with cell cycle regulation in epithelial cells.Biochemical pharmacology · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic disease predominantly caused by alteration or dysregulation of the PKD1 gene, which encodes polycystin-1 (PC1). The disease is characterized by the progressive expansion of bilateral fluid-filled renal cysts that ultimately lead to renal failure. Individual cysts, even within patients with germline mutations, are genetically heterogeneous, displaying diverse chromosomal abnormalities. To date, the molecular mechanisms responsible for this genetic heterogeneity remain unknown. Using a lentiviral-mediated siRNA expression model of Pkd1 hypomorphism, we show that loss of PC1 function is sufficient to produce centrosome amplification and multipolar spindle formation. These events lead to genomic instability characterized by gross polyploidism and mitotic catastrophe. Following these dramatic early changes, the cell population rapidly converges toward a stable ploidy in which centrosome amplification is significantly decreased, though cytological abnormalities such as micronucleation, chromatin bridges and aneuploidy remain common. In agreement with our in vitro findings, we provide the first in vivo evidence that significant centrosome amplification occurs in kidneys from conditional Pkd1 knockout mice at early and late time during the disease progression as well as in human ADPKD patients. These findings establish a novel function of PC1 in ADPKD pathogenesis and a genetic mechanism that may underlie the intrafamilial variability of ADPKD progression.
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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.