ArticleProceedings of the National Academy of Sciences of the United States of America2014
Nedd9 restrains renal cystogenesis in Pkd1-/- mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- In-depth analysis of obesity-associated changes in adipose tissue-derived mesenchymal stromal/stem cells and primary cilia function.Communications biology · 2025Article
- Isorhapontigenin Inhibits Cell Growth, Angiogenesis, Migration, and Invasion of Non-Small-Cell Lung Cancer Cells Through NEDD9 Signaling.International journal of molecular sciences · 2025Article
- Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice.Nature communications · 2024Article
- Loss of Pkd1 limits susceptibility to colitis and colorectal cancer.Oncogenesis · 2023Article
- Patterns of Ciliation and Ciliary Signaling in Cancer.Reviews of physiology, biochemistry and pharmacology · 2023Review
- NEDD9 Restrains dsDNA Damage Response during Non-Small Cell Lung Cancer (NSCLC) Progression.Cancers · 2022Article
- Review
- Review
- Modeling Neoplastic Growth in Renal Cell Carcinoma and Polycystic Kidney Disease.International journal of molecular sciences · 2021Review
- Intraflagellar Transport Proteins as Regulators of Primary Cilia Length.Frontiers in cell and developmental biology · 2021Review
- Primary Cilia and Calcium Signaling Interactions.International journal of molecular sciences · 2020Review
- Loss of polycystins suppresses deciliation via the activation of the centrosomal integrity pathway.Life science alliance · 2020Article
- Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease.Cellular signalling · 2020Review
- Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Microscopy-Based Automated Live Cell Screening for Small Molecules That Affect Ciliation.Frontiers in genetics · 2019Article
- Exploring genetic modifiers of Gaucher disease: The next horizon.Human mutation · 2018Review
- Ciliary signalling in cancer.Nature reviews. Cancer · 2018Review
- Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- From Peas to Disease: Modifier Genes, Network Resilience, and the Genetics of Health.American journal of human genetics · 2017Review
- Mechanisms for nonmitotic activation of Aurora-A at cilia.Biochemical Society transactions · 2017Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations inactivating the cilia-localized Pkd1 protein result in autosomal dominant polycystic kidney disease (ADPKD), a serious inherited syndrome affecting ∼ 1 in 500 people, in which accumulation of renal cysts eventually destroys kidney function. Severity of ADPKD varies throughout the population, for reasons thought to involve differences both in intragenic Pkd1 mutations and in modifier alleles. The scaffolding protein NEDD9, commonly dysregulated during cancer progression, interacts with Aurora-A (AURKA) kinase to control ciliary resorption, and with Src and other partners to influence proliferative signaling pathways often activated in ADPKD. We here demonstrate Nedd9 expression is deregulated in human ADPKD and a mouse ADPKD model. Although genetic ablation of Nedd9 does not independently influence cystogenesis, constitutive absence of Nedd9 strongly promotes cyst formation in the tamoxifen-inducible Pkd1fl/fl;Cre/Esr1(+) mouse model of ADPKD. This cystogenic effect is associated with striking morphological defects in the cilia of Pkd1(-/-);Nedd9(-/-) mice, associated with specific loss of ciliary localization of adenylase cyclase III in the doubly mutant genotype. Ciliary phenotypes imply a failure of Aurora-A activation: Compatible with this idea, Pkd1(-/-);Nedd9(-/-) mice had ciliary resorption defects, and treatment of Pkd1(-/-) mice with a clinical Aurora-A kinase inhibitor exacerbated cystogenesis. In addition, activation of the ADPKD-associated signaling effectors Src, Erk, and the mTOR effector S6 was enhanced, and Ca(2+) response to external stimuli was reduced, in Pkd1(-/-);Nedd9(-/-) versus Pkd1(-/-) mice. Together, these results indicated an important modifier action of Nedd9 on ADPKD pathogenesis involving failure to activate Aurora-A.
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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.