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Genetics. Jul 2000; 155(3): 1231–1244.
PMCID: PMC1461160

Ariadne-1: a vital Drosophila gene is required in development and defines a new conserved family of ring-finger proteins.

Abstract

We report the identification and functional characterization of ariadne-1 (ari-1), a novel and vital Drosophila gene required for the correct differentiation of most cell types in the adult organism. Also, we identify a sequence-related gene, ari-2, and the corresponding mouse and human homologues of both genes. All these sequences define a new protein family by the Acid-rich, RING finger, B-box, RING finger, coiled-coil (ARBRCC) motif string. In Drosophila, ari-1 is expressed throughout development in all tissues. The mutant phenotypes are most noticeable in cells that undergo a large and rapid membrane deposition, such as rewiring neurons during metamorphosis, large tubular muscles during adult myogenesis, and photoreceptors. Occasional survivors of null alleles exhibit reduced life span, motor impairments, and short and thin bristles. Single substitutions at key cysteines in each RING finger cause lethality with no survivors and a drastic reduction of rough endoplasmic reticulum that can be observed in the photoreceptors of mosaic eyes. In yeast two-hybrid assays, the protein ARI-1 interacts with a novel ubiquitin-conjugating enzyme, UbcD10, whose sequence is also reported here. The N-terminal RING-finger motif is necessary and sufficient to mediate this interaction. Mouse and fly homologues of both ARI proteins and the Ubc can substitute for each other in the yeast two-hybrid assay, indicating that ARI represents a conserved novel mechanism in development. In addition to ARI homologues, the RBR signature is also found in the Parkinson-disease-related protein Parkin adjacent to an ubiquitin-like domain, suggesting that the study of this mechanism could be relevant for human pathology.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alves-Rodrigues A, Gregori L, Figueiredo-Pereira ME. Ubiquitin, cellular inclusions and their role in neurodegeneration. Trends Neurosci. 1998 Dec;21(12):516–520. [PubMed]
  • Baldwin AS., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. [PubMed]
  • Barlow PN, Luisi B, Milner A, Elliott M, Everett R. Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger. J Mol Biol. 1994 Mar 25;237(2):201–211. [PubMed]
  • Baumann A, Krah-Jentgens I, Müller R, Müller-Holtkamp F, Seidel R, Kecskemethy N, Casal J, Ferrus A, Pongs O. Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an I(A) channel transcript with homology to vertebrate Na channel. EMBO J. 1987 Nov;6(11):3419–3429. [PMC free article] [PubMed]
  • Blest AD. A new method for the reduced silver impregnation of arthropod central nervous systems. Proc R Soc Lond B Biol Sci. 1976 Apr 13;193(1111):191–197. [PubMed]
  • Bordallo J, Plemper RK, Finger A, Wolf DH. Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol Biol Cell. 1998 Jan;9(1):209–222. [PMC free article] [PubMed]
  • Borden KL, Freemont PS. The RING finger domain: a recent example of a sequence-structure family. Curr Opin Struct Biol. 1996 Jun;6(3):395–401. [PubMed]
  • Borden KL, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 1995 Apr 3;14(7):1532–1541. [PMC free article] [PubMed]
  • Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG, Jr, Elledge SJ, Conaway RC, et al. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science. 1999 Apr 23;284(5414):657–661. [PubMed]
  • Brzovic PS, Meza J, King MC, Klevit RE. The cancer-predisposing mutation C61G disrupts homodimer formation in the NH2-terminal BRCA1 RING finger domain. J Biol Chem. 1998 Apr 3;273(14):7795–7799. [PubMed]
  • Kang HY, Yeh S, Fujimoto N, Chang C. Cloning and characterization of human prostate coactivator ARA54, a novel protein that associates with the androgen receptor. J Biol Chem. 1999 Mar 26;274(13):8570–8576. [PubMed]
  • Canal I, Fariñas CI, Gho M, Ferrús A. The presynaptic cell determines the number of synapses in the Drosophila optic ganglia. Eur J Neurosci. 1994 Sep 1;6(9):1423–1431. [PubMed]
  • Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605–608. [PubMed]
  • Carthew RW, Rubin GM. seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eye. Cell. 1990 Nov 2;63(3):561–577. [PubMed]
  • Klug A, Schwabe JW. Protein motifs 5. Zinc fingers. FASEB J. 1995 May;9(8):597–604. [PubMed]
  • Cenci G, Rawson RB, Belloni G, Castrillon DH, Tudor M, Petrucci R, Goldberg ML, Wasserman SA, Gatti M. UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior. Genes Dev. 1997 Apr 1;11(7):863–875. [PubMed]
  • Koegl M, Hoppe T, Schlenker S, Ulrich HD, Mayer TU, Jentsch S. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell. 1999 Mar 5;96(5):635–644. [PubMed]
  • Colley NJ, Baker EK, Stamnes MA, Zuker CS. The cyclophilin homolog ninaA is required in the secretory pathway. Cell. 1991 Oct 18;67(2):255–263. [PubMed]
  • Landschulz WH, Johnson PF, McKnight SL. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. [PubMed]
  • Coombe PE, Heisenberg M. The structural brain mutant Vacuolar medulla of Drosophila melanogaster with specific behavioral defects and cell degeneration in the adult. J Neurogenet. 1986 May;3(3):135–158. [PubMed]
  • Liakopoulos D, Doenges G, Matuschewski K, Jentsch S. A novel protein modification pathway related to the ubiquitin system. EMBO J. 1998 Apr 15;17(8):2208–2214. [PMC free article] [PubMed]
  • Desterro JM, Thomson J, Hay RT. Ubch9 conjugates SUMO but not ubiquitin. FEBS Lett. 1997 Nov 17;417(3):297–300. [PubMed]
  • Drummond DR, Hennessey ES, Sparrow JC. Characterisation of missense mutations in the Act88F gene of Drosophila melanogaster. Mol Gen Genet. 1991 Apr;226(1-2):70–80. [PubMed]
  • Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences. Science. 1991 May 24;252(5009):1162–1164. [PubMed]
  • Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN, Solomon E, de Thé H, Hay RT, Freemont PS. SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation. J Cell Sci. 1999 Feb;112(Pt 3):381–393. [PubMed]
  • Martinez-Noel G, Niedenthal R, Tamura T, Harbers K. A family of structurally related RING finger proteins interacts specifically with the ubiquitin-conjugating enzyme UbcM4. FEBS Lett. 1999 Jul 9;454(3):257–261. [PubMed]
  • Edgecomb RS, Ghetti C, Schneiderman AM. Bendless alters thoracic musculature in Drosophila. J Neurogenet. 1993 Apr;8(4):201–219. [PubMed]
  • Matuschewski K, Hauser HP, Treier M, Jentsch S. Identification of a novel family of ubiquitin-conjugating enzymes with distinct amino-terminal extensions. J Biol Chem. 1996 Feb 2;271(5):2789–2794. [PubMed]
  • Everett RD, Earnshaw WC, Findlay J, Lomonte P. Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. EMBO J. 1999 Mar 15;18(6):1526–1538. [PMC free article] [PubMed]
  • Ferrús A, Llamazares S, de la Pompa JL, Tanouye MA, Pongs O. Genetic analysis of the Shaker gene complex of Drosophila melanogaster. Genetics. 1990 Jun;125(2):383–398. [PMC free article] [PubMed]
  • Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N. Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1996 Feb 29;3(1):17–24. [PubMed]
  • Freemont PS. The RING finger. A novel protein sequence motif related to the zinc finger. Ann N Y Acad Sci. 1993 Jun 11;684:174–192. [PubMed]
  • Fujita SC, Zipursky SL, Benzer S, Ferrús A, Shotwell SL. Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7929–7933. [PMC free article] [PubMed]
  • Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M. Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5. J Biol Chem. 1996 Feb 2;271(5):2795–2800. [PubMed]
  • Harbers K, Müller U, Grams A, Li E, Jaenisch R, Franz T. Provirus integration into a gene encoding a ubiquitin-conjugating enzyme results in a placental defect and embryonic lethality. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12412–12417. [PMC free article] [PubMed]
  • Oh CE, McMahon R, Benzer S, Tanouye MA. bendless, a Drosophila gene affecting neuronal connectivity, encodes a ubiquitin-conjugating enzyme homolog. J Neurosci. 1994 May;14(5 Pt 2):3166–3179. [PubMed]
  • Hattori N, Matsumine H, Asakawa S, Kitada T, Yoshino H, Elibol B, Brookes AJ, Yamamura Y, Kobayashi T, Wang M, et al. Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the Parkin gene. Biochem Biophys Res Commun. 1998 Aug 28;249(3):754–758. [PubMed]
  • Okumoto K, Itoh R, Shimozawa N, Suzuki Y, Tamura S, Kondo N, Fujiki Y. Mutations in PEX10 is the cause of Zellweger peroxisome deficiency syndrome of complementation group B. Hum Mol Genet. 1998 Sep;7(9):1399–1405. [PubMed]
  • Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425–479. [PubMed]
  • Prado A, Canal I, Barbas JA, Molloy J, Ferrús A. Functional recovery of troponin I in a Drosophila heldup mutant after a second site mutation. Mol Biol Cell. 1995 Nov;6(11):1433–1441. [PMC free article] [PubMed]
  • Hu G, Fearon ER. Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins. Mol Cell Biol. 1999 Jan;19(1):724–732. [PMC free article] [PubMed]
  • Prado A, Canal I, Ferrús A. The haplolethal region at the 16F gene cluster of Drosophila melanogaster: structure and function. Genetics. 1999 Jan;151(1):163–175. [PMC free article] [PubMed]
  • Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Jun 30;5(3):169–176. [PubMed]
  • Price BD, Chang Z, Smith R, Bockheim S, Laughon A. The Drosophila neuralized gene encodes a C3HC4 zinc finger. EMBO J. 1993 Jun;12(6):2411–2418. [PMC free article] [PubMed]
  • Jensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM, Tommerup N, Vissing H, Sekido Y, et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene. 1998 Mar 5;16(9):1097–1112. [PubMed]
  • Reddy BA, Etkin LD. A unique bipartite cysteine-histidine motif defines a subfamily of potential zinc-finger proteins. Nucleic Acids Res. 1991 Nov 25;19(22):6330–6330. [PMC free article] [PubMed]
  • Reddy BA, Etkin LD, Freemont PS. A novel zinc finger coiled-coil domain in a family of nuclear proteins. Trends Biochem Sci. 1992 Sep;17(9):344–345. [PubMed]
  • Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science. 1999 Apr 23;284(5414):662–665. [PubMed]
  • Régnier CH, Tomasetto C, Moog-Lutz C, Chenard MP, Wendling C, Basset P, Rio MC. Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma. J Biol Chem. 1995 Oct 27;270(43):25715–25721. [PubMed]
  • Tranque P, Crossin KL, Cirelli C, Edelman GM, Mauro VP. Identification and characterization of a RING zinc finger gene (C-RZF) expressed in chicken embryo cells. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3105–3109. [PMC free article] [PubMed]
  • Triezenberg SJ. Structure and function of transcriptional activation domains. Curr Opin Genet Dev. 1995 Apr;5(2):190–196. [PubMed]
  • Tyers M, Willems AR. One ring to rule a superfamily of E3 ubiquitin ligases. Science. 1999 Apr 23;284(5414):601–604. [PubMed]
  • Saurin AJ, Borden KL, Boddy MN, Freemont PS. Does this have a familiar RING? Trends Biochem Sci. 1996 Jun;21(6):208–214. [PubMed]

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