Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1995 Jul 1;130(1):1–13. doi: 10.1083/jcb.130.1.1

Molecular characterization of NDP52, a novel protein of the nuclear domain 10, which is redistributed upon virus infection and interferon treatment

PMCID: PMC2120522  PMID: 7540613

Abstract

The nuclear domain (ND)10 also described as POD or Kr bodies is involved in the development of acute promyelocytic leukemia and virus- host interactions. Immunofluorescence analysis using a variety of human autoimmune sera and monoclonal antibodies showed a typical dot like nuclear staining for ND10, suggesting that this structure consists of several proteins. Two of the ND10 proteins, Sp100 and PML are genetically characterized and show homology with several transcription factors. Here we describe NDP52, an additional novel protein of the ND10. We raised a new mAb C8A2, that specifically recognizes NDP52. Immunofluorescence analysis using this mAb showed a typical nuclear dot staining as it was described for ND10. Isolation and sequencing of the corresponding cDNA revealed that NDP52 has a predicted molecular mass of 52 kD. The deduced amino acid sequence exhibits an extended central coiled coil domain containing a leucine zipper motif. The COOH terminus of NDP52 shows homology with LIM domains, that have recently been described to mediate protein interactions, which let NDP52 appear as a suitable candidate for mediating interactions between ND10 proteins. In vivo, NDP52 is transcribed in all human tissues analyzed. Furthermore, we show that NDP52 colocalizes with the ND10 protein PML and can be redistributed upon viral infection and interferon treatment. These data suggest that ND10 proteins play an important role in the viral life cycle.

Full Text

The Full Text of this article is available as a PDF (3.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoniou M., Carmo-Fonseca M., Ferreira J., Lamond A. I. Nuclear organization of splicing snRNPs during differentiation of murine erythroleukemia cells in vitro. J Cell Biol. 1993 Dec;123(5):1055–1068. doi: 10.1083/jcb.123.5.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ascoli C. A., Maul G. G. Identification of a novel nuclear domain. J Cell Biol. 1991 Mar;112(5):785–795. doi: 10.1083/jcb.112.5.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baltz R., Domon C., Pillay D. T., Steinmetz A. Characterization of a pollen-specific cDNA from sunflower encoding a zinc finger protein. Plant J. 1992 Sep;2(5):713–721. [PubMed] [Google Scholar]
  4. Bridge E., Carmo-Fonseca M., Lamond A., Pettersson U. Nuclear organization of splicing small nuclear ribonucleoproteins in adenovirus-infected cells. J Virol. 1993 Oct;67(10):5792–5802. doi: 10.1128/jvi.67.10.5792-5802.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Busch S. J., Sassone-Corsi P. Dimers, leucine zippers and DNA-binding domains. Trends Genet. 1990 Feb;6(2):36–40. doi: 10.1016/0168-9525(90)90071-d. [DOI] [PubMed] [Google Scholar]
  6. Castaigne S., Chomienne C., Daniel M. T., Ballerini P., Berger R., Fenaux P., Degos L. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704–1709. [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Cohen C., Parry D. A. Alpha-helical coiled coils and bundles: how to design an alpha-helical protein. Proteins. 1990;7(1):1–15. doi: 10.1002/prot.340070102. [DOI] [PubMed] [Google Scholar]
  9. Crawford A. W., Michelsen J. W., Beckerle M. C. An interaction between zyxin and alpha-actinin. J Cell Biol. 1992 Mar;116(6):1381–1393. doi: 10.1083/jcb.116.6.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dingwall C., Laskey R. A. Nuclear targeting sequences--a consensus? Trends Biochem Sci. 1991 Dec;16(12):478–481. doi: 10.1016/0968-0004(91)90184-w. [DOI] [PubMed] [Google Scholar]
  11. Dyck J. A., Maul G. G., Miller W. H., Jr, Chen J. D., Kakizuka A., Evans R. M. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell. 1994 Jan 28;76(2):333–343. doi: 10.1016/0092-8674(94)90340-9. [DOI] [PubMed] [Google Scholar]
  12. Eckert R. L., Green H. Structure and evolution of the human involucrin gene. Cell. 1986 Aug 15;46(4):583–589. doi: 10.1016/0092-8674(86)90884-6. [DOI] [PubMed] [Google Scholar]
  13. Everett R. D. Construction and characterization of herpes simplex virus type 1 mutants with defined lesions in immediate early gene 1. J Gen Virol. 1989 May;70(Pt 5):1185–1202. doi: 10.1099/0022-1317-70-5-1185. [DOI] [PubMed] [Google Scholar]
  14. Everett R. D., Maul G. G. HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J. 1994 Nov 1;13(21):5062–5069. doi: 10.1002/j.1460-2075.1994.tb06835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fakan S., Leser G., Martin T. E. Ultrastructural distribution of nuclear ribonucleoproteins as visualized by immunocytochemistry on thin sections. J Cell Biol. 1984 Jan;98(1):358–363. doi: 10.1083/jcb.98.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fu X. D., Maniatis T. Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus. Nature. 1990 Feb 1;343(6257):437–441. doi: 10.1038/343437a0. [DOI] [PubMed] [Google Scholar]
  17. Goddard A. D., Borrow J., Freemont P. S., Solomon E. Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science. 1991 Nov 29;254(5036):1371–1374. doi: 10.1126/science.1720570. [DOI] [PubMed] [Google Scholar]
  18. Guldner H. H., Szostecki C., Grötzinger T., Will H. IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. J Immunol. 1992 Dec 15;149(12):4067–4073. [PubMed] [Google Scholar]
  19. Kakizuka A., Miller W. H., Jr, Umesono K., Warrell R. P., Jr, Frankel S. R., Murty V. V., Dmitrovsky E., Evans R. M. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663–674. doi: 10.1016/0092-8674(91)90112-c. [DOI] [PubMed] [Google Scholar]
  20. Kastner P., Perez A., Lutz Y., Rochette-Egly C., Gaub M. P., Durand B., Lanotte M., Berger R., Chambon P. Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. EMBO J. 1992 Feb;11(2):629–642. doi: 10.1002/j.1460-2075.1992.tb05095.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Koken M. H., Puvion-Dutilleul F., Guillemin M. C., Viron A., Linares-Cruz G., Stuurman N., de Jong L., Szostecki C., Calvo F., Chomienne C. The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J. 1994 Mar 1;13(5):1073–1083. doi: 10.1002/j.1460-2075.1994.tb06356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Korioth F., Gieffers C., Frey J. Cloning and characterization of the human gene encoding aspartyl beta-hydroxylase. Gene. 1994 Dec 15;150(2):395–399. doi: 10.1016/0378-1119(94)90460-x. [DOI] [PubMed] [Google Scholar]
  23. Kosa J. L., Michelsen J. W., Louis H. A., Olsen J. I., Davis D. R., Beckerle M. C., Winge D. R. Common metal ion coordination in LIM domain proteins. Biochemistry. 1994 Jan 18;33(2):468–477. doi: 10.1021/bi00168a011. [DOI] [PubMed] [Google Scholar]
  24. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  25. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  26. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  27. Laskey R. A., Dingwall C. Nuclear shuttling: the default pathway for nuclear proteins? Cell. 1993 Aug 27;74(4):585–586. doi: 10.1016/0092-8674(93)90505-k. [DOI] [PubMed] [Google Scholar]
  28. Lupas A., Van Dyke M., Stock J. Predicting coiled coils from protein sequences. Science. 1991 May 24;252(5009):1162–1164. doi: 10.1126/science.252.5009.1162. [DOI] [PubMed] [Google Scholar]
  29. Martelli A. M., Gilmour R. S., Bertagnolo V., Neri L. M., Manzoli L., Cocco L. Nuclear localization and signalling activity of phosphoinositidase C beta in Swiss 3T3 cells. Nature. 1992 Jul 16;358(6383):242–245. doi: 10.1038/358242a0. [DOI] [PubMed] [Google Scholar]
  30. Maul G. G., Everett R. D. The nuclear location of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICP0. J Gen Virol. 1994 Jun;75(Pt 6):1223–1233. doi: 10.1099/0022-1317-75-6-1223. [DOI] [PubMed] [Google Scholar]
  31. Maul G. G., Guldner H. H., Spivack J. G. Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J Gen Virol. 1993 Dec;74(Pt 12):2679–2690. doi: 10.1099/0022-1317-74-12-2679. [DOI] [PubMed] [Google Scholar]
  32. Peters R. Fluorescence microphotolysis to measure nucleocytoplasmic transport and intracellular mobility. Biochim Biophys Acta. 1986 Dec 22;864(3-4):305–359. doi: 10.1016/0304-4157(86)90003-1. [DOI] [PubMed] [Google Scholar]
  33. Pombo A., Ferreira J., Bridge E., Carmo-Fonseca M. Adenovirus replication and transcription sites are spatially separated in the nucleus of infected cells. EMBO J. 1994 Nov 1;13(21):5075–5085. doi: 10.1002/j.1460-2075.1994.tb06837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Puvion E., Viron A., Assens C., Leduc E. H., Jeanteur P. Immunocytochemical identification of nuclear structures containing snRNPs in isolated rat liver cells. J Ultrastruct Res. 1984 May;87(2):180–189. doi: 10.1016/s0022-5320(84)80077-5. [DOI] [PubMed] [Google Scholar]
  35. Rice R. H., Green H. Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell. 1979 Nov;18(3):681–694. doi: 10.1016/0092-8674(79)90123-5. [DOI] [PubMed] [Google Scholar]
  36. Sadler I., Crawford A. W., Michelsen J. W., Beckerle M. C. Zyxin and cCRP: two interactive LIM domain proteins associated with the cytoskeleton. J Cell Biol. 1992 Dec;119(6):1573–1587. doi: 10.1083/jcb.119.6.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Samuel C. E. Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities. Virology. 1991 Jul;183(1):1–11. doi: 10.1016/0042-6822(91)90112-o. [DOI] [PubMed] [Google Scholar]
  38. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schmeichel K. L., Beckerle M. C. The LIM domain is a modular protein-binding interface. Cell. 1994 Oct 21;79(2):211–219. doi: 10.1016/0092-8674(94)90191-0. [DOI] [PubMed] [Google Scholar]
  40. Schmidt-Zachmann M. S., Dargemont C., Kühn L. C., Nigg E. A. Nuclear export of proteins: the role of nuclear retention. Cell. 1993 Aug 13;74(3):493–504. doi: 10.1016/0092-8674(93)80051-f. [DOI] [PubMed] [Google Scholar]
  41. Simon M., Green H. The glutamine residues reactive in transglutaminase-catalyzed cross-linking of involucrin. J Biol Chem. 1988 Dec 5;263(34):18093–18098. [PubMed] [Google Scholar]
  42. Smith T. F., Waterman M. S. Identification of common molecular subsequences. J Mol Biol. 1981 Mar 25;147(1):195–197. doi: 10.1016/0022-2836(81)90087-5. [DOI] [PubMed] [Google Scholar]
  43. Spector D. L. Macromolecular domains within the cell nucleus. Annu Rev Cell Biol. 1993;9:265–315. doi: 10.1146/annurev.cb.09.110193.001405. [DOI] [PubMed] [Google Scholar]
  44. Spector D. L., Schrier W. H., Busch H. Immunoelectron microscopic localization of snRNPs. Biol Cell. 1983;49(1):1–10. doi: 10.1111/j.1768-322x.1984.tb00215.x. [DOI] [PubMed] [Google Scholar]
  45. Struhl K. Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eukaryotic transcriptional regulatory proteins. Trends Biochem Sci. 1989 Apr;14(4):137–140. doi: 10.1016/0968-0004(89)90145-X. [DOI] [PubMed] [Google Scholar]
  46. Stuurman N., de Graaf A., Floore A., Josso A., Humbel B., de Jong L., van Driel R. A monoclonal antibody recognizing nuclear matrix-associated nuclear bodies. J Cell Sci. 1992 Apr;101(Pt 4):773–784. doi: 10.1242/jcs.101.4.773. [DOI] [PubMed] [Google Scholar]
  47. Szostecki C., Guldner H. H., Netter H. J., Will H. Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. J Immunol. 1990 Dec 15;145(12):4338–4347. [PubMed] [Google Scholar]
  48. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Visa N., Puvion-Dutilleul F., Bachellerie J. P., Puvion E. Intranuclear distribution of U1 and U2 snRNAs visualized by high resolution in situ hybridization: revelation of a novel compartment containing U1 but not U2 snRNA in HeLa cells. Eur J Cell Biol. 1993 Apr;60(2):308–321. [PubMed] [Google Scholar]
  50. Wadman I., Li J., Bash R. O., Forster A., Osada H., Rabbitts T. H., Baer R. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J. 1994 Oct 17;13(20):4831–4839. doi: 10.1002/j.1460-2075.1994.tb06809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Weis K., Rambaud S., Lavau C., Jansen J., Carvalho T., Carmo-Fonseca M., Lamond A., Dejean A. Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell. 1994 Jan 28;76(2):345–356. doi: 10.1016/0092-8674(94)90341-7. [DOI] [PubMed] [Google Scholar]
  52. Xie K., Lambie E. J., Snyder M. Nuclear dot antigens may specify transcriptional domains in the nucleus. Mol Cell Biol. 1993 Oct;13(10):6170–6179. doi: 10.1128/mcb.13.10.6170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zhang G., Taneja K. L., Singer R. H., Green M. R. Localization of pre-mRNA splicing in mammalian nuclei. Nature. 1994 Dec 22;372(6508):809–812. doi: 10.1038/372809a0. [DOI] [PubMed] [Google Scholar]
  54. de Thé H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. doi: 10.1016/0092-8674(91)90113-d. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES