Nuclear bodies explained

Nuclear bodies (also known as nuclear domains, or nuclear dots) are membraneless structures found in the cell nuclei of eukaryotic cells.[1] Nuclear bodies include Cajal bodies, the nucleolus, nuclear speckles (also called splicing speckles), histone locus bodies, and promyelocytic leukemia protein (PML) nuclear bodies (also called PML oncogenic dots).[2] Nuclear bodies also include ND10s. ND stands for nuclear domain, and 10 refers to the number of dots seen.[3]

Nuclear bodies were first seen as prominent interchromatin structures in the nuclei of malignant or hyperstimulated animal cells[4] [5] identified using anti-sp100 autoantibodies from primary biliary cirrhosis and subsequently the promyelocytic leukemia (PML) factor, but appear also to be elevated in many autoimmune and cancerous diseases.[6] Nuclear dots are metabolically stable and resistant to nuclease digestion and salt extraction.[7]

A nuclear body subtype is a clastosome suggested to be a site of protein degradation.[8]

Structure

Simple nuclear bodies (types I and II) and the shells of complex nuclear bodies (types III, IVa and V) consist of a non-chromatinic fibrillar material which is most likely proteinaceous.[9] That nuclear bodies co-isolated with the nuclear matrix, and were linked to the fibrogranular nuclear matrix component by projections from the surface of the nuclear bodies.[9] The primary components of the nuclear dots are the proteins sp100 nuclear antigen, LYSP100(a homolog of sp100),[10] ISG20,[11] PML antigen, NDP55 and 53kDa protein associated with the nuclear matrix.[12] Other proteins, such as PIC1/SUMO-1, which are associated with nuclear pore complex also associate with nuclear dots.[13] The proteins can reorganize in the nucleus, by increasing number of dispersion in response to different stress (stimulation or heat shock, respectively).[14]

Function

One of the nuclear body proteins appears to be involved in transcriptional active regions.[15] Expression of PML antigen and sp100 is responsive to interferons. Sp100 seems to have transcriptional transactivating properties. PML protein was reported to suppress growth and transformation,[5] and specifically inhibits the infection of vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus,[16] but not other types of viruses. The SUMO-1 ubiquitin like protein is responsible for modifying PML protein such that it is targeted to dots.[17] whereas overexpression of PML results in programmed cell death.[18]

One hypothesized function of the dots is as a 'nuclear dump' or 'storage depot'.[19] The nuclear bodies may not all perform the same function. Sp140 associates with certain bodies and appears to be involved in transcriptional activation.[20]

ND10 nuclear bodies have been shown to play a major role in chromatin regulation.[21]

Pathology

These, or similar, bodies have been found increased in the presence of lymphoid cancers[22] [23] and SLE (lupus).[24] They are also observed at higher frequencies insubacute sclerosing panencephalitis

in this instance, antibodies to measles show expression in and localization to the nuclear bodies.[25]

Notes and References

  1. Weber SC . Sequence-encoded material properties dictate the structure and function of nuclear bodies . Current Opinion in Cell Biology . 46 . 62–71 . June 2017 . 28343140 . 10.1016/j.ceb.2017.03.003 .
  2. Zimber A, Nguyen QD, Gespach C . Nuclear bodies and compartments: functional roles and cellular signalling in health and disease . Cellular Signalling . 16 . 10 . 1085–104 . October 2004 . 15240004 . 10.1016/j.cellsig.2004.03.020 .
  3. Rivera-Molina YA, Martínez FP, Tang Q . Nuclear domain 10 of the viral aspect . World Journal of Virology . 2 . 3 . 110–22 . August 2013 . 24255882 . 3832855 . 10.5501/wjv.v2.i3.110 . free .
  4. Brasch K, Ochs RL . Nuclear bodies (NBs): a newly "rediscovered" organelle . Experimental Cell Research . 202 . 2 . 211–23 . October 1992 . 1397076 . 10.1016/0014-4827(92)90068-J .
  5. Sternsdorf T, Grötzinger T, Jensen K, Will H . Nuclear dots: actors on many stages . Immunobiology . 198 . 1–3 . 307–31 . December 1997 . 9442402 . 10.1016/s0171-2985(97)80051-4 .
  6. Pawlotsky JM, Andre C, Metreau JM, Beaugrand M, Zafrani ES, Dhumeaux D . Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis . Hepatology . 16 . 1 . 127–31 . July 1992 . 1319948 . 10.1002/hep.1840160121 . 22729443 .
  7. Ascoli CA, Maul GG . Identification of a novel nuclear domain . The Journal of Cell Biology . 112 . 5 . 785–95 . March 1991 . 1999457 . 2288866 . 10.1083/jcb.112.5.785 .
  8. Lafarga M, Berciano MT, Pena E, Mayo I, Castaño JG, Bohmann D, Rodrigues JP, Tavanez JP, Carmo-Fonseca M . 6 . Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome . Molecular Biology of the Cell . 13 . 8 . 2771–82 . August 2002 . 12181345 . 117941 . 10.1091/mbc.e02-03-0122 .
  9. Chaly N, Setterfield G, Kaplan JG, Brown DL . Nuclear bodies in mouse splenic lymphocytes: II - Cytochemistry and autoradiography during stimulation by concanavalin A . Biology of the Cell . 49 . 1 . 35–43 . 1983 . 6199062 . 10.1111/j.1768-322x.1984.tb00220.x . 43084163 .
  10. Dent AL, Yewdell J, Puvion-Dutilleul F, Koken MH, de The H, Staudt LM . LYSP100-associated nuclear domains (LANDs): description of a new class of subnuclear structures and their relationship to PML nuclear bodies . Blood . 88 . 4 . 1423–6 . August 1996 . 8695863 . 10.1182/blood.V88.4.1423.bloodjournal8841423. free .
  11. Gongora C, David G, Pintard L, Tissot C, Hua TD, Dejean A, Mechti N . Molecular cloning of a new interferon-induced PML nuclear body-associated protein . The Journal of Biological Chemistry . 272 . 31 . 19457–63 . August 1997 . 9235947 . 10.1074/jbc.272.31.19457 . free .
  12. Zuber M, Heyden TS, Lajous-Petter AM . A human autoantibody recognizing nuclear matrix-associated nuclear protein localized in dot structures . Biology of the Cell . 85 . 1 . 77–86 . 1995 . 8882521 . 10.1111/j.1768-322X.1995.tb00944.x .
  13. Sternsdorf T, Jensen K, Will H . Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1 . The Journal of Cell Biology . 139 . 7 . 1621–34 . December 1997 . 9412458 . 2132645 . 10.1083/jcb.139.7.1621 .
  14. Maul GG, Yu E, Ishov AM, Epstein AL . Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress . Journal of Cellular Biochemistry . 59 . 4 . 498–513 . December 1995 . 8749719 . 10.1002/jcb.240590410 . 22209911 .
  15. Xie K, Lambie EJ, Snyder M . Nuclear dot antigens may specify transcriptional domains in the nucleus . Molecular and Cellular Biology . 13 . 10 . 6170–9 . October 1993 . 8413218 . 364676 . 10.1128/MCB.13.10.6170 .
  16. Chelbi-Alix MK, Quignon F, Pelicano L, Koken MH, de Thé H . Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein . Journal of Virology . 72 . 2 . 1043–51 . February 1998 . 9444998 . 124576 . 10.1128/JVI.72.2.1043-1051.1998.
  17. Müller S, Matunis MJ, Dejean A . Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus . The EMBO Journal . 17 . 1 . 61–70 . January 1998 . 9427741 . 1170358 . 10.1093/emboj/17.1.61 .
  18. Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC, de Thé H . PML induces a novel caspase-independent death process . Nature Genetics . 20 . 3 . 259–65 . November 1998 . 9806544 . 10.1038/3068 . 856232 .
  19. Maul GG . Nuclear domain 10, the site of DNA virus transcription and replication . BioEssays . 20 . 8 . 660–7 . August 1998 . 9780840 . 10.1002/(SICI)1521-1878(199808)20:8<660::AID-BIES9>3.0.CO;2-M . 46499841 .
  20. Bloch DB, Chiche JD, Orth D, de la Monte SM, Rosenzweig A, Bloch KD . Structural and functional heterogeneity of nuclear bodies . Molecular and Cellular Biology . 19 . 6 . 4423–30 . June 1999 . 10330182 . 104401 . 10.1128/MCB.19.6.4423 .
  21. Gu H, Zheng Y . Role of ND10 nuclear bodies in the chromatin repression of HSV-1 . Virology Journal . 13 . 62 . April 2016 . 27048561 . 4822283 . 10.1186/s12985-016-0516-4 . free .
  22. Rivas C, Oliva H . Nuclear bodies in Hodgkin's disease . Pathologia Europaea . 9 . 4 . 297–301 . 1974 . 4457783 .
  23. Book: Tani E, Ametani T . Nuclear Characteristics of Malignant Lymphoma in the Brain . Malignant Lymphomas of the Nervous System . Acta Neuropathologica. Supplementum . Suppl 6 . 167–71 . 1975 . 168720 . 10.1007/978-3-662-08456-4_28. 978-3-540-07208-9 .
  24. Jones JM, Martinez AJ, Joshi VV, McWilliams N . Systemic lupus erythematosus . Archives of Pathology . 99 . 3 . 152–7 . March 1975 . 164172 .
  25. Brown HR, Thormar H . Immunoperoxidase staining of simple nuclear bodies in sclerosing panencephalitis (SSPE) by antiserum to Measles nucleocapsids . Acta Neuropathologica . 36 . 3 . 259–67 . November 1976 . 795259 . 10.1007/BF00685370 . 38057985 .
  26. Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D, Grignani F, Pelicci PG, Testi R . 6 . Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein . Blood . 92 . 7 . 2244–51 . October 1998 . 9746761 .
  27. Schneider SM, Pritchard SM, Wudiri GA, Trammell CE, Nicola AV . Early Steps in Herpes Simplex Virus Infection Blocked by a Proteasome Inhibitor . mBio . 10 . 3 . e00732–19, /mbio/10/3/mBio.00732–19.atom . May 2019 . 31088925 . 6520451 . 10.1128/mBio.00732-19 . Terence S. . Dermody .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Nuclear bodies".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.