The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation (132 views) (PDF restricted 26 views)
Embo J (ISSN: 0261-4189linking), 2021 May 17; 40(10): e106503-N/D.
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Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 9.96, 5-year impact factor: 10.4
Url: Not available.
Keywords: Ofd1 , Pka , Praja2 , Primary Cilium , Ubiquitin,
Affiliations:
*** IBB - CNR ***
Department of Molecular Medicine and Medical Biotechnologies, University Federico II, Naples, Italy.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Institute of Biostructures and Bioimaging, CNR, Naples, Italy.
Department of Pharmacy, University Federico II, Naples, Italy.
Net4Science srl, University "Magna Graecia", Catanzaro, Italy.
Department of Biology, University Federico II, Naples, Italy.
Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria.
Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
Tyrolean Cancer Research Institute, Innsbruck, Austria.
Department of Translational Medical Science, University Federico II, Naples, Italy.
References:
Not available.
Embo J (ISSN: 0261-4189linking), 2021 May 17; 40(10): e106503-N/D.
Export to BibTeX Export to EndNote
Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 9.96, 5-year impact factor: 10.4
Url: Not available.
Keywords: Ofd1 , Pka , Praja2 , Primary Cilium , Ubiquitin,
Affiliations:
*** IBB - CNR ***
Department of Molecular Medicine and Medical Biotechnologies, University Federico II, Naples, Italy.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Institute of Biostructures and Bioimaging, CNR, Naples, Italy.
Department of Pharmacy, University Federico II, Naples, Italy.
Net4Science srl, University "Magna Graecia", Catanzaro, Italy.
Department of Biology, University Federico II, Naples, Italy.
Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria.
Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
Tyrolean Cancer Research Institute, Innsbruck, Austria.
Department of Translational Medical Science, University Federico II, Naples, Italy.
References:
Not available.
The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation
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.
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.
The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation
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The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation
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View Export to BibTeX Export to EndNote
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Impact Factor: 8.668
View Export to BibTeX Export to EndNote
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Impact Factor: 4.069
View Export to BibTeX Export to EndNote
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* New comprehensive studies of a gold(III) Dithiocarbamate complex with proven anticancer properties: Aqueous dissolution with cyclodextrins, pharmacokinetics and upstream inhibition of the ubiquitin-proteasome pathway (961 views)
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Impact Factor: 4.816
View Export to BibTeX Export to EndNote
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* Multiple functions of insulin-degrading enzyme: a metabolic crosslight? (487 views)
Crit Rev Biochem Mol (ISSN: 1040-9238), 2017 Jun; N/D: 1-29.
Impact Factor: 5.279
View Export to BibTeX Export to EndNote
Lanza V, Travaglia A, Malgieri G, Fattorusso R, GrassoG, Di Natale G, Zito V, Arena G, Milardi D, Rizzarelli E
* Ubiquitin Associates with the N-Terminal Domain of Nerve Growth Factor: The Role of Copper(II) Ions (366 views) (PDF 188 views)
Chemistry (ISSN: 0947-6539, 1521-3765, 1521-3765electronic), 2016 Dec 05; 22(49): 17767-17775.
Impact Factor: 5.317
View Export to BibTeX Export to EndNote
Barone D, Balasco N, Vitagliano L
* KCTD5 is endowed with large, functionally relevant, interdomain motions (295 views)
J Biomol Struct Dyn (ISSN: 0739-1102, 1538-0254electronic, 0739-1102linking), 2016 Aug; 34(8): 1725-1735.
Impact Factor: 3.123
View Export to BibTeX Export to EndNote
GrassoG, Lanza V, Malgieri G, Fattorusso R, Pietropaolo A, Rizzarelli E, Milardi D
* The insulin degrading enzyme activates ubiquitin and promotes the formation of K48 and K63 diubiquitin (430 views) (PDF 221 views)
Chem Commun (ISSN: 1359-7345, 1364-548x, 1364-548xelectronic), 2015 Nov 7; 51(86): 15724-15727.
Impact Factor: 6.567
View Export to BibTeX Export to EndNote
Ruggiero A, Squeglia F, Romano M, Vitagliano L, De Simone A, Berisio R
* The structure of Resuscitation promoting factor B from M. tuberculosis reveals unexpected ubiquitin-like domains (468 views)
Bba-Gen Subjects (ISSN: 0005-2728, 0006-3002print, 1570-9639print), 2015 Nov 5; 1860(2): 445-451.
Impact Factor: 4.864
View Export to BibTeX Export to EndNote
Smaldone G, Pirone L, Balasco N, Di Gaetano S, Pedone E, Vitagliano L
* Cullin 3 recognition is not a universal property among KCTD proteins (991 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2015 May 14; 10(5): e0126808-e0126808.
Impact Factor: 3.057
View Export to BibTeX Export to EndNote
Correale S, de Paola I, Morgillo CM, Federico A, Zaccaro L, Pallante P, Galeone A, Fusco A, Pedone E, Luque FJ, Catalanotti B
* Structural Model of the hUbA1-UbcH10 Quaternary Complex: In Silico and Experimental Analysis of the Protein-Protein Interactions between E1, E2 and Ubiquitin (636 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2014 Nov 6; 9(11): e112082-e112082.
Impact Factor: 3.234
View Export to BibTeX Export to EndNote
Balasco N, Pirone L, Smaldone G, Di Gaetano S, Esposito L, Pedone E, Vitagliano L
* Molecular recognition of Cullin3 by KCTDs: Insights from experimental and computational investigations (578 views)
Bba-Gen Subjects (ISSN: 0925-4439, 0006-3002, 1570-9639), 2014 Jul; 1844(7): 1289-1298.
Impact Factor: 4.882
View Export to BibTeX Export to EndNote
Arena G, Bellia F, Frasca G, Grasso G, Lanza V, Rizzarelli E, Tabbì G, Zito V, Milardi D
* Inorganic stressors of ubiquitin (422 views) (PDF 222 views)
Inorg Chem (ISSN: 1520-510x, 1520-510xelectronic, 0020-1669linking), 2013 Sep 19; 52(16): 9567-9573.
Impact Factor: 4.794
View Export to BibTeX Export to EndNote
Lignitto L, Arcella A, Sepe M, Rinaldi L, Delle Donne R, Gallo A, Stefan E, Bachmann VA, Oliva MA, Tiziana Storlazzi C, L'Abbate A, Brunetti A, Gargiulo S, Gramanzini M, Insabato L, Garbi C, Gottesman ME, Feliciello A
* Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth (625 views)
Nat Commun (ISSN: 2041-1723, 2041-1723electronic, 2041-1723linking), 2013 May; 4: 100-105.
Impact Factor: 10.742
View Export to BibTeX Export to EndNote
Buanne P, Renzone G, Monteleone F, Vitale M, Monti SM, Sandomenico A, Garbi C, Montanaro D, Accardo M, Troncone G, Zatovicova M, Csaderova L, Supuran CT, Pastorekova S, Scaloni A, De Simone G, Zambrano N
* Characterization of carbonic anhydrase ix interactome reveals proteins assisting its nuclear localization in hypoxic cells (549 views)
J Proteome Res (ISSN: 1535-3893), 2013 Jan; 12(1): 282-292.
Impact Factor: 5.001
View Export to BibTeX Export to EndNote
Poletto M, Vascotto C, Scognamiglio PL, Lirussi L, Marasco D, Tell G
* Role Of The Unstructured N-Terminal Domain Of The Human Apurinic/Apyrimidinic Endonuclease 1 (hape1) In The Modulation Of Its Interaction With Nucleic Acids And Nucleophosmin (npm1) (555 views)
Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking), 2013; 452(3): 545-557.
Impact Factor: 4.779
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Pirone L, Esposito C, Correale S, Graziano G, Di Gaetano S, Vitagliano L, Pedone E
* Thermal and chemical stability of two homologous POZ/BTB domains of KCTD proteins characterized by a different oligomeric organization (610 views)
Biomed Res Int (ISSN: 2314-6133, 2314-6141, 2314-6141electronic), 2013; 2013: 162674-162674.
Impact Factor: 1.579
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Riccio A, Cubellis MV
* Gain of function in CDKN1C (576 views)
Nature Genetics (ISSN: 1061-4036), 2012 Jul; 44(7): 737-738.
Impact Factor: 35.209
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Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E, Calabrese EJ
* Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity (5441 views)
Bba-Gen Subjects (ISSN: 0006-3002, 0925-4439, 1570-9639), 2012 May; 1822(5): 753-783.
Impact Factor: 3.733
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Palmieri G, Bergamo P, Luini A, Ruvo M, Gogliettino M, Langella E, Saviano M, Hegde RN, Sandomenico A, Rossi M
* Acylpeptide hydrolase inhibition as targeted strategy to induce proteasomal down-regulation (820 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2011 Oct 10; 6(10): e25888-e25888.
Impact Factor: 4.092
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Arena G, Fattorusso R, Grasso G, Grasso GI, Isernia C, Malgieri G, Milardi D, Rizzarelli E
* Zinc(II) complexes of ubiquitin: speciation, affinity and binding features (784 views)
Chemistry (ISSN: 1521-3765, 0947-6539, 1521-3765electronic), 2011 Oct 4; 17(41): 11596-11603.
Impact Factor: 5.925
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Pirone L, Correale S, De Paola I, Zaccaro L, De Simone G, Vitagliano L, Pedone E, Di Gaetano S
* Design, synthesis and characterization of a peptide able to bind proteins of the KCTD family: implications for KCTD - cullin 3 recognition (513 views)
J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print), 2011 May; 17(5): 373-376.
Impact Factor: 1.799
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Correale S, Pirone L, Di Marcotullio L, De Smaele E, Greco A, Mazzà D, Moretti M, Alterio V, Vitagliano L, Di Gaetano S, Gulino A, Pedone E
* Molecular organization of the cullin E3 ligase adaptor KCTD11 (716 views)
Biochimie (ISSN: 0300-9084, 1638-6183, 1638-6183electronic), 2011 Apr; 93(4): 715-724.
Impact Factor: 3.022
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Canettieri G, Di Marcotullio L, Greco A, Coni S, Antonucci L, Infante P, Pietrosanti L, De Smaele E, Ferretti E, Miele E, Pelloni M, De Simone G, Pedone E, Gallinari P, Giorgi A, Steinkuhler C, Vitagliano L, Pedone C, Schinin ME, Screpanti I, Gulino A
* Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation (920 views)
Nature Cell Biol Nature Cell Biology (ISSN: 1476-4679, 1465-7392), 2010 Feb; 12(2): 132-142.
Impact Factor: 19.407
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Galasso G, De Rosa R, Piscione F, Iaccarino G, Vosa C, Sorriento D, Piccolo R, Rapacciuolo A, Walsh K, Chiariello M
* Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure (444 views)
Eur J Heart Fail European Journal Of Heart Failure (ISSN: 1388-9842), 2010; 12(12): 1290-1296.
Impact Factor: 4.512
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Arnesano F, Scintilla S, Calò V, Bonfrate E, Ingrosso C, Losacco M, Pellegrino T, Rizzarelli E, Natile G
* Copper-triggered aggregation of ubiquitin (670 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2009 Sep 16; 4(9): e7052-e7052.
Impact Factor: 4.351
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Grasso G, Rizzarelli E, Spoto G
* How the binding and degrading capabilities of insulin degrading enzyme are affected by ubiquitin (445 views)
Bba-Gen Subjects (ISSN: 0006-3002, 1570-9639, 0925-4439), 2008 Jul; 1784(7-8): 1122-1126.
Impact Factor: 2.233
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Pellecchia MT, Varrone A, Annesi G, Amboni M, Cicarelli G, Sansone V, Annesi F, Rocca FE, Vitale C, Pappata S, Quattrone A, Barone P
* Parkinsonism and essential tremor in a family with pseudo-dominant inheritance of PARK2: An FP-CIT SPECT study (524 views)
Mov Disord (ISSN: 0885-3185, 1531-8257, 0885-3185linking), 2007 Mar 15; 22(4): 559-563.
Impact Factor: 3.207
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Milardi D, Arnesano F, Grasso G, Magrì A, Tabbì G, Scintilla S, Natile G, Rizzarelli E
* Ubiquitin stability and the Lys63-linked polyubiquitination site are compromised on copper binding (486 views)
Angew Chem Int Ed (ISSN: 1433-7851, 1521-3773electronic, 1433-7851linking), 2007; 46(42): 7993-7995.
Impact Factor: 10.031
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Sciacca MFM, Milardi D, Pappalardo M, La Rosa C, Grasso DM
* Role of electrostatics in the thermal stability of ubiquitin: A combined DSC and MM study (336 views)
Journal Of Thermal Analysis And Calorimetry (ISSN: 1388-6150), 2006 Nov; 86(2): 311-314.
Impact Factor: 1.438
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Santelli E, Leone M, Li C, Fukushima T, Preece NE, Olson AJ, Ely KR, Reed JC, Pellecchia M, Liddington RC, Matsuzawa S-I
* Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex (846 views)
Jbc Papers (ISSN: 0021-9258, 1083-351x, 0021-9258linking), 2005 Oct 7; 280(40): 34278-34287.
Impact Factor: 5.854
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Varrone A, Pellecchia MT, Amboni M, Sansone V, Salvatore E, Ghezzi D, Garavaglia B, Brice A, Brunetti A, Bonavita V, De Michele G, Salvatore M, Pappata S, Barone P
* Imaging of dopaminergic dysfunction with [123I]FP-CIT SPECT in early-onset parkin disease (4281 views)
Neurology (ISSN: 0028-3878, 1526-632x, 1526-632xelectronic), 2004 Dec 14; 63(11): 2097-2103.
Impact Factor: 5.973
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32 Records (30 excluding Abstracts).
Total impact factor: 196.278 (188.693 excluding Abstracts).
Total 5 year impact factor: 199.14 (191.055 excluding Abstracts).
Total impact factor: 196.278 (188.693 excluding Abstracts).
Total 5 year impact factor: 199.14 (191.055 excluding Abstracts).
132 views. Last view on Saturday 12 October 2024, 18:15:06
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