ArticleThe EMBO journal2021
The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Identification of the first peptide inhibitor of UBE2C enzymatic activity: insights from metadynamics-guided folding and binding studies.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Genomic early growth mechanisms of two endangered Mexican spruces.BMC plant biology · 2026Article
- Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5.Nature chemical biology · 2026Article
- Sexually distinct multi-omic responses to progressive endurance exercise training in the rat lung.American journal of respiratory cell and molecular biology · 2026Article
- Phosphosite-centric regulatory network of ATAD2 and its involvement in transcriptional networks.Molecular genetics and genomics : MGG · 2026Article
- Reshaping cancer cell plasticity by P-body dynamics and protein translation.Communications biology · 2026Review
- Structure and assembly of the A-C linker connecting microtubule triplets in centrioles.Science advances · 2025Article
- CCHCR1 links P-body proteins to the centrosome and is required for ciliogenesis through interacting with OFD1 and PCM1.Cellular & molecular biology letters · 2025Article
- The A-C linker controls centriole structural integrity and duplication.Nature communications · 2025Article
- Insights into golgi apparatus and centrosome: implications for ciliogenesis.Molecular biology reports · 2025Review
- PJA2 Suppresses Colorectal Cancer Progression by Controlling HDAC2 Degradation and Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Conservation of OFD1 Protein Motifs: Implications for Discovery of Novel Interactors and the OFD1 Function.International journal of molecular sciences · 2025Article
- A Novel Pathogenic Splicing Mutation ofPharmacogenomics and personalized medicine · 2025Article
- Genomic Amplification of TBC1D31 Promotes Hepatocellular Carcinoma Through Reducing the Rab22A-Mediated Endolysosomal Trafficking and Degradation of EGFR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unveiling differential gene co-expression networks and its effects on levodopa-induced dyskinesia.iScience · 2024Article
- TBC1 domain-containing proteins are frequently involved in triple-negative breast cancers in connection with the induction of a glycolytic phenotype.Cell death & disease · 2024Article
- Phosphorylation of the compartmentalized PKA substrate TAF15 regulates RNA-protein interactions.Cellular and molecular life sciences : CMLS · 2024Article
- Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer.Communications biology · 2024Article
- Functional Divergence and Origin of the Vertebrate Praja Family.Journal of molecular evolution · 2024Article
- KCTD1 is a new modulator of the KCASH family of Hedgehog suppressors.Neoplasia (New York, N.Y.) · 2023Article
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
The primary cilium is a microtubule-based sensory organelle that dynamically links signalling pathways to cell differentiation, growth, and development. Genetic defects of primary cilia are responsible for genetic disorders known as ciliopathies. Orofacial digital type I syndrome (OFDI) is an X-linked congenital ciliopathy caused by mutations in the OFD1 gene and characterized by malformations of the face, oral cavity, digits and, in the majority of cases, polycystic kidney disease. OFD1 plays a key role in cilium biogenesis. However, the impact of signalling pathways and the role of the ubiquitin-proteasome system (UPS) in the control of OFD1 stability remain unknown. Here, we identify a novel complex assembled at centrosomes by TBC1D31, including the E3 ubiquitin ligase praja2, protein kinase A (PKA), and OFD1. We show that TBC1D31 is essential for ciliogenesis. Mechanistically, upon G-protein-coupled receptor (GPCR)-cAMP stimulation, PKA phosphorylates OFD1 at ser735, thus promoting OFD1 proteolysis through the praja2-UPS circuitry. This pathway is essential for ciliogenesis. In addition, a non-phosphorylatable OFD1 mutant dramatically affects cilium morphology and dynamics. Consistent with a role of the TBC1D31/praja2/OFD1 axis in ciliogenesis, alteration of this molecular network impairs ciliogenesis in vivo in Medaka fish, resulting in developmental defects. Our findings reveal a multifunctional transduction unit at the centrosome that links GPCR signalling to ubiquitylation and proteolysis of the ciliopathy protein OFD1, with important implications on cilium biology and development. Derangement of this control mechanism may underpin human genetic disorders.
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