ArticleHuman molecular genetics2014
SIRT2 regulates ciliogenesis and contributes to abnormal centrosome amplification caused by loss of polycystin-1.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Post-Translational Modifications in Cilia and Ciliopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Ultrastructure expansion microscopy (U-ExM) of mouse and human kidneys for analysis of subcellular structures.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Sonic Hedgehog activates prostaglandin signaling to stabilize primary cilium length.The Journal of cell biology · 2024Article
- Article
- Inhibiting centrosome clustering reduces cystogenesis and improves kidney function in autosomal dominant polycystic kidney disease.JCI insight · 2024Article
- Computational drug discovery approaches identify mebendazole as a candidate treatment for autosomal dominant polycystic kidney disease.Frontiers in pharmacology · 2024Article
- Folate conjugated nanomedicines for selective inhibition of mTOR signaling in polycystic kidneys at clinically relevant doses.Biomaterials · 2023Article
- Review
- Measuring potential effects of the developmental burden associated with the vertebrate notochord.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD.Frontiers in molecular biosciences · 2022Review
- Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna.Frontiers in cellular neuroscience · 2022Review
- 2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells.Molecules (Basel, Switzerland) · 2021Article
- Epigenetically Mediated Ciliogenesis and Cell Cycle Regulation, and Their Translational Potential.Cells · 2021Review
- Roles for ELMOD2 and Rootletin in ciliogenesis.Molecular biology of the cell · 2021Article
- Primary Cilia in Glial Cells: An Oasis in the Journey to Overcoming Neurodegenerative Diseases.Frontiers in neuroscience · 2021Review
- Loss of Deacetylation Enzymes Hdac6 and Sirt2 Promotes Acetylation of Cytoplasmic Tubulin, but Suppresses Axonemal Acetylation in Zebrafish Cilia.Frontiers in cell and developmental biology · 2021Article
- Biallelic loss of function NEK3 mutations deacetylate α-tubulin and downregulate NUP205 that predispose individuals to cilia-related abnormal cardiac left-right patterning.Cell death & disease · 2020Article
- Polycystin-1 regulates ARHGAP35-dependent centrosomal RhoA activation and ROCK signaling.JCI insight · 2020Article
- Epigenetics and cell cycle regulation in cystogenesis.Cellular signalling · 2020Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
The mechanisms underlying many of the human disease phenotypes associated with ciliary dysfunction and abnormal centrosome amplification have yet to be fully elucidated. Here, we present for the first time that SIRT2, a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, regulates ciliogenesis and centrosome amplification. Overexpression of SIRT2 in renal epithelial cells appeared to disrupt cilia formation, causing decreased numbers of cells with cilia and decreased cilia length, while inhibition of SIRT2 activity by nicotinamide treatment or knockdown of SIRT2 with siRNA was shown to block cilia disassembly during the cell cycle. Overexpression of SIRT2 in zebrafish decreased cilia numbers in Kupffer's vesicle, while morpholino knock down of SIRT2 increased cilia length. Aberrant centrosome amplification and polyploidy were seen with overexpression of SIRT2 in mouse inner medullary collecting duct 3 cells, similar to that observed following Pkd1 knockdown. SIRT2 was up-regulated in both Pkd1 mutant and knockdown cells. Depletion of SIRT2 prevented the abnormal centrosome amplification and polyploidy associated with loss of polycystin-1 (PC1) alone. Thus, we conclude that the aberrant centrosome amplification and polyploidy in Pkd1 mutant or depleted cells was mediated through overexpression of SIRT2. Our results suggest a novel function of SIRT2 in cilia dynamics and centrosome function, and in ciliopathy-associated disease progression.
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