intranuclear inclusion bodies

Summary

Summary: Circumscribed masses of foreign or metabolically inactive materials, within the CELL NUCLEUS. Some are VIRAL INCLUSION BODIES.

Top Publications

  1. Tavalai N, Stamminger T. New insights into the role of the subnuclear structure ND10 for viral infection. Biochim Biophys Acta. 2008;1783:2207-21 pubmed publisher
  2. Weidtkamp Peters S, Lenser T, Negorev D, Gerstner N, Hofmann T, Schwanitz G, et al. Dynamics of component exchange at PML nuclear bodies. J Cell Sci. 2008;121:2731-43 pubmed publisher
    ..These findings provide a kinetics model for factor exchange at PML NBs and highlight potential mechanisms to regulate intranuclear trafficking of specific factors at these domains...
  3. Dellaire G, Bazett Jones D. PML nuclear bodies: dynamic sensors of DNA damage and cellular stress. Bioessays. 2004;26:963-77 pubmed
    ..The dramatically increased total surface area available would enhance interactions between PML-associated factors regulating DNA repair and apoptosis...
  4. Lallemand Breitenbach V, De The H. PML nuclear bodies. Cold Spring Harb Perspect Biol. 2010;2:a000661 pubmed publisher
    ..Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma...
  5. Wojciechowska M, Krzyzosiak W. Cellular toxicity of expanded RNA repeats: focus on RNA foci. Hum Mol Genet. 2011;20:3811-21 pubmed publisher
  6. Osterwald S, Wörz S, Reymann J, Sieckmann F, Rohr K, Erfle H, et al. A three-dimensional colocalization RNA interference screening platform to elucidate the alternative lengthening of telomeres pathway. Biotechnol J. 2012;7:103-16 pubmed publisher
    ..It extends the available repertoire of high-content screening to studies of cellular colocalizations and allows the identification of candidate genes for the ALT mechanism that represent possible targets for cancer therapy...
  7. Mackenzie I, Baker M, West G, Woulfe J, Qadi N, Gass J, et al. A family with tau-negative frontotemporal dementia and neuronal intranuclear inclusions linked to chromosome 17. Brain. 2006;129:853-67 pubmed
  8. Sivachandran N, Sarkari F, Frappier L. Epstein-Barr nuclear antigen 1 contributes to nasopharyngeal carcinoma through disruption of PML nuclear bodies. PLoS Pathog. 2008;4:e1000170 pubmed publisher
    ..The results point to an important role for EBNA1 in the development of NPC, in which EBNA1-mediated disruption of PML nuclear bodies promotes the survival of cells with DNA damage. ..
  9. Fasching C, Neumann A, Muntoni A, Yeager T, Reddel R. DNA damage induces alternative lengthening of telomeres (ALT) associated promyelocytic leukemia bodies that preferentially associate with linear telomeric DNA. Cancer Res. 2007;67:7072-7 pubmed
    ..We partially purified APBs and showed that the telomeric repeat DNA they contain is predominantly linear. We propose that a function of APBs is to sequester linear telomeric DNA...

More Information

Publications62

  1. Ching R, Dellaire G, Eskiw C, Bazett Jones D. PML bodies: a meeting place for genomic loci?. J Cell Sci. 2005;118:847-54 pubmed
    ..Moreover, PML bodies associate with specific regions of high transcriptional activity in the cellular genome. We propose that PML bodies functionally interact with chromatin and are important for the regulation of gene expression...
  2. Daughters R, Tuttle D, Gao W, Ikeda Y, Moseley M, Ebner T, et al. RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet. 2009;5:e1000600 pubmed publisher
  3. Carmo Fonseca M, Rino J. RNA seeds nuclear bodies. Nat Cell Biol. 2011;13:110-2 pubmed publisher
    ..Now, two live-cell imaging studies provide compelling evidence that nascent RNAs can act as transiently immobilized scaffolds that recruit specific nuclear body proteins...
  4. Gao C, Ho C, Reineke E, Lam M, Cheng X, Stanya K, et al. Histone deacetylase 7 promotes PML sumoylation and is essential for PML nuclear body formation. Mol Cell Biol. 2008;28:5658-67 pubmed publisher
    ..Importantly, HDAC7 knockdown inhibits tumor necrosis factor alpha-induced PML sumoylation and the formation of PML NBs in HUVECs. These results demonstrate a novel function of HDAC7 and provide a regulatory mechanism of PML sumoylation...
  5. Shishido Hara Y. Progressive multifocal leukoencephalopathy and promyelocytic leukemia nuclear bodies: a review of clinical, neuropathological, and virological aspects of JC virus-induced demyelinating disease. Acta Neuropathol. 2010;120:403-17 pubmed publisher
    ..Here, we review what we have learned since the disease entity establishment, including a look at recent progress in understanding the relationship between JC virus, etiology and PML-NBs...
  6. Silva Fernandes A, Costa M, Duarte Silva S, Oliveira P, Botelho C, Martins L, et al. Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiol Dis. 2010;40:163-76 pubmed publisher
    ..We propose the transgenic CMVMJD94 mice as a useful model to study the early stages in the pathogenesis of MJD and to explore the molecular mechanisms involved in CAG repeat instability...
  7. Woulfe J. Nuclear bodies in neurodegenerative disease. Biochim Biophys Acta. 2008;1783:2195-206 pubmed publisher
    ..Although research in this field is in its infancy, identifying alterations in the nucleus in neurodegenerative disease has potentially profound implications for elucidating the pathogenesis of these disorders...
  8. Mohamad N, Boden M. The proteins of intra-nuclear bodies: a data-driven analysis of sequence, interaction and expression. BMC Syst Biol. 2010;4:44 pubmed publisher
    ..While the nucleolus and nuclear speckles have received more attention experimentally, the PML nuclear body and the Cajal body are still incompletely characterized in terms of their roles and protein complement...
  9. Rüb U, de Vos R, Brunt E, Sebesteny T, Schols L, Auburger G, et al. Spinocerebellar ataxia type 3 (SCA3): thalamic neurodegeneration occurs independently from thalamic ataxin-3 immunopositive neuronal intranuclear inclusions. Brain Pathol. 2006;16:218-27 pubmed
    ..This lack of correlation may suggest that ataxin-3 immunopositive NI are not immediately decisive for the fate of affected nerve cells but rather represent unspecific and pathognomonic morphological markers of SCA3...
  10. Frappier L. Viral disruption of promyelocytic leukemia (PML) nuclear bodies by hijacking host PML regulators. Virulence. 2011;2:58-62 pubmed
    ..The results suggest that EBNA1 usurps two host PML regulators in order to promote degradation of PML proteins and loss of PML NBs. ..
  11. Cioce M, Lamond A. Cajal bodies: a long history of discovery. Annu Rev Cell Dev Biol. 2005;21:105-31 pubmed
    ..We speculate on the relationship between CB function and molecular disease...
  12. Zimber A, Nguyen Q, Gespach C. Nuclear bodies and compartments: functional roles and cellular signalling in health and disease. Cell Signal. 2004;16:1085-104 pubmed
    ..The objective of this review is to summarize some aspects of these nuclear structures/bodies/domains, including their proposed roles in cellular signalling and in human diseases, mainly neurodegenerative disorders and cancer...
  13. Wang S, Long J, Zheng C. The potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1. Protein Cell. 2012;3:372-82 pubmed publisher
    ..In this review, we discuss the fundamentals of the interaction between ICP0 and PML NBs, suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1...
  14. Bond C, Fox A. Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol. 2009;186:637-44 pubmed publisher
    ..Given the large numbers of long noncoding transcripts currently being discovered through whole transcriptome analysis, paraspeckles may be a paradigm for a class of subnuclear bodies formed around long noncoding RNA...
  15. Cho G, Lim Y, Golden J. SUMO interaction motifs in Sizn1 are required for promyelocytic leukemia protein nuclear body localization and for transcriptional activation. J Biol Chem. 2009;284:19592-600 pubmed publisher
    ..Taken together, our data indicate that the SIMs in Sizn1 are required for its PML-NB localization and for the full transcriptional co-activation function in BMP signaling...
  16. Sunwoo H, Dinger M, Wilusz J, Amaral P, Mattick J, Spector D. MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res. 2009;19:347-59 pubmed publisher
    ..Our findings indicate that the MEN epsilon/beta non-coding RNAs are essential structural/organizational components of paraspeckles. ..
  17. Boy J, Schmidt T, Schumann U, Grasshoff U, Unser S, Holzmann C, et al. A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats. Neurobiol Dis. 2010;37:284-93 pubmed publisher
    ..Few and small intranuclear aggregates appeared first at the age of 18 months, further supporting the claim that neuronal dysfunction precedes the formation of intranuclear aggregates...
  18. Sharma P, Murillas R, Zhang H, Kuehn M. N4BP1 is a newly identified nucleolar protein that undergoes SUMO-regulated polyubiquitylation and proteasomal turnover at promyelocytic leukemia nuclear bodies. J Cell Sci. 2010;123:1227-34 pubmed publisher
    ..These findings suggest a dynamic interaction between subnuclear compartments, and a role for post-translational modification by ubiquitin and SUMO in the regulation of nucleolar protein turnover...
  19. Difiglia M, Sena Esteves M, Chase K, Sapp E, Pfister E, Sass M, et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl Acad Sci U S A. 2007;104:17204-9 pubmed
  20. Bernardi R, Pandolfi P. Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol. 2007;8:1006-16 pubmed
    ..Recent data suggest that PML-NBs may be heterogeneous in composition, mobility and function...
  21. Dellaire G, Eskiw C, Dehghani H, Ching R, Bazett Jones D. Mitotic accumulations of PML protein contribute to the re-establishment of PML nuclear bodies in G1. J Cell Sci. 2006;119:1034-42 pubmed
    ..The recycling of PML protein from one cell cycle to the next via mitotic accumulations may represent a common mechanism for the partitioning of other nuclear bodies during mitosis...
  22. Wilburn B, Rudnicki D, Zhao J, Weitz T, Cheng Y, Gu X, et al. An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. Neuron. 2011;70:427-40 pubmed publisher
    ..These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2...
  23. Chung I, Leonhardt H, Rippe K. De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. J Cell Sci. 2011;124:3603-18 pubmed publisher
    ..X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway...
  24. Jeanne M, Lallemand Breitenbach V, Ferhi O, Koken M, Le Bras M, Duffort S, et al. PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3. Cancer Cell. 2010;18:88-98 pubmed publisher
    ..Thus, PML oxidation regulates NB-biogenesis, while oxidation-enforced PML/RARA multimerization and direct arsenic-binding cooperate to enforce APL's exquisite As(2)O(3) sensitivity...
  25. Mao Y, Sunwoo H, Zhang B, Spector D. Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol. 2011;13:95-101 pubmed publisher
    ..This study establishes a model in which Men ?/? ncRNAs serve as a platform to recruit proteins to assemble paraspeckles...
  26. Jiang M, Entezami P, Gamez M, Stamminger T, Imperiale M. Functional reorganization of promyelocytic leukemia nuclear bodies during BK virus infection. MBio. 2011;2:e00281-10 pubmed publisher
    ..We hypothesize that the antiviral functions of PML-NBs are inactivated through reorganization during normal BKV infection...
  27. Shishido Hara Y, Ichinose S, Uchihara T. JC virus intranuclear inclusions associated with PML-NBs: analysis by electron microscopy and structured illumination microscopy. Am J Pathol. 2012;180:1095-106 pubmed publisher
    ..Either the agnogene or its product likely supports efficient progeny production at PML-NBs, leading to subsequent degeneration of host glial cells...
  28. Lucchiari S, Pagliarani S, Corti S, Mancinelli E, Servida M, Fruguglietti E, et al. Colocalization of ribonuclear inclusions with muscle blind like-proteins in a family with myotonic dystrophy type 2 associated with a short CCTG expansion. J Neurol Sci. 2008;275:159-63 pubmed publisher
    ..This is one of the smallest expansion reported and the shortest with the evidence of nuclear foci. These data contribute to the clinical and molecular correlation of ZNF9 gene short expansion...
  29. Wang J, Shiels C, Sasieni P, Wu P, Islam S, Freemont P, et al. Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions. J Cell Biol. 2004;164:515-26 pubmed
    ..We propose that PML bodies form in nuclear compartments of high transcriptional activity, but they do not directly regulate transcription of genes in these compartments...
  30. Wang Y, Liu W, Wada E, Murata M, Wada K, Kanazawa I. Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA. Neurosci Res. 2005;53:241-9 pubmed
    ..Treatments using this siRNA significantly prolonged model mice longevity, improved motor function and slowed down the loss of body weight. This work suggests that siRNA-based therapy is promising as a future treatment for HD...
  31. Qin Q, Inatome R, Hotta A, Kojima M, Yamamura H, Hirai H, et al. A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein. J Cell Biol. 2006;172:497-504 pubmed
    ..We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases...
  32. Heun P. SUMOrganization of the nucleus. Curr Opin Cell Biol. 2007;19:350-5 pubmed
    ..Related functions include the organization of chromatin loops and maintenance of rDNA repeat stability. Consequently, complete loss of SUMO modification profoundly affects nuclear organization and cell viability...
  33. Tassone F, Iwahashi C, Hagerman P. FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor/ataxia syndrome (FXTAS). RNA Biol. 2004;1:103-5 pubmed
    ..Consistent with this model, we have now identified FMR1 mRNA within the intranuclear inclusions isolated from post-mortem (FXTAS) brain tissue...
  34. Dror N, Rave Harel N, Burchert A, Azriel A, Tamura T, Tailor P, et al. Interferon regulatory factor-8 is indispensable for the expression of promyelocytic leukemia and the formation of nuclear bodies in myeloid cells. J Biol Chem. 2007;282:5633-40 pubmed
    ..When IRF-8 levels are compromised, the reduced PML expression may lead to genome instability and eventually to the leukemic phenotype...
  35. Sivachandran N, Cao J, Frappier L. Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to disrupt PML nuclear bodies. J Virol. 2010;84:11113-23 pubmed publisher
    ..The combined results indicate that EBNA1 usurps two independent cellular pathways to trigger the loss of PML NBs. ..
  36. Goti D, Katzen S, Mez J, Kurtis N, Kiluk J, Ben Haïem L, et al. A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration. J Neurosci. 2004;24:10266-79 pubmed
  37. Fu L, Gao Y, Sztul E. Transcriptional repression and cell death induced by nuclear aggregates of non-polyglutamine protein. Neurobiol Dis. 2005;20:656-65 pubmed
    ..Our results indicate that nuclear aggregation and transcriptional effects are not unique to polyQ-containing proteins and may represent a general response to misfolded proteins in the nucleus...
  38. Reichelt M, Wang L, Sommer M, Perrino J, Nour A, Sen N, et al. Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus. PLoS Pathog. 2011;7:e1001266 pubmed publisher
    ..The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins...
  39. Shevtsov S, Dundr M. Nucleation of nuclear bodies by RNA. Nat Cell Biol. 2011;13:167-73 pubmed publisher
    ..Together, these data suggest that RNA-primed biogenesis of nuclear bodies is a general principle of nuclear organization...
  40. Stagno d Alcontres M, Mendez Bermudez A, Foxon J, Royle N, Salomoni P. Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA. J Cell Biol. 2007;179:855-67 pubmed
    ..Finally, we find a substantial loss of telomeric DNA upon stable TRF2 knockdown in ALT cells. Overall, we provide insight into the functional consequences of shelterin alterations in ALT cells...
  41. Lang M, Jegou T, Chung I, Richter K, Münch S, Udvarhelyi A, et al. Three-dimensional organization of promyelocytic leukemia nuclear bodies. J Cell Sci. 2010;123:392-400 pubmed publisher
    ..From our findings, we derived a model that explains how the three-dimensional organization of PML-NBs serves to concentrate different biological activities while allowing for an efficient exchange of components...
  42. Gialitakis M, Arampatzi P, Makatounakis T, Papamatheakis J. Gamma interferon-dependent transcriptional memory via relocalization of a gene locus to PML nuclear bodies. Mol Cell Biol. 2010;30:2046-56 pubmed publisher
    ..We propose that the primary signal-induced transcription generates spatial and epigenetic memory that is maintained through several cell generations and endows the cell with increased responsiveness to future activation signals...
  43. Mankodi A, Teng Umnuay P, Krym M, Henderson D, Swanson M, Thornton C. Ribonuclear inclusions in skeletal muscle in myotonic dystrophy types 1 and 2. Ann Neurol. 2003;54:760-8 pubmed
    ..We conclude that ribonuclear inclusions are a key feature of the muscle pathology in DM and that sequestration of muscleblind proteins may have a direct role in the disease process...
  44. Everett R, Chelbi Alix M. PML and PML nuclear bodies: implications in antiviral defence. Biochimie. 2007;89:819-30 pubmed
    ..This article reviews the potential antiviral activities of PML NB constituent proteins, how RNA and DNA viruses overcome these defences, and the connections between these events and IFN pathways...
  45. Lloret A, Dragileva E, Teed A, Espinola J, Fossale E, Gillis T, et al. Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice. Hum Mol Genet. 2006;15:2015-24 pubmed
    ..Our findings set the stage for defining disease-related genetic pathways that will ultimately provide insight into disease mechanism...
  46. Fu C, Ahmed K, Ding H, Ding X, Lan J, Yang Z, et al. Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3. Oncogene. 2005;24:5401-13 pubmed
    ..Taken together, our studies provide first line of evidence showing that SUMO-3 is essential for PML localization and offer novel insight into the pathobiochemistry of APL...
  47. Jegou T, Chung I, Heuvelman G, Wachsmuth M, Görisch S, Greulich Bode K, et al. Dynamics of telomeres and promyelocytic leukemia nuclear bodies in a telomerase-negative human cell line. Mol Biol Cell. 2009;20:2070-82 pubmed publisher
    ..Based on these studies, a model is proposed in which the shortening of telomeres results in an increased mobility that could facilitate the formation of complexes between telomeres and PML-NBs...
  48. Clemson C, Hutchinson J, Sara S, Ensminger A, Fox A, Chess A, et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 2009;33:717-26 pubmed publisher
    ..Collectively, results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain...
  49. Reineke E, Kao H. Targeting promyelocytic leukemia protein: a means to regulating PML nuclear bodies. Int J Biol Sci. 2009;5:366-76 pubmed
    ..This review focuses on the current knowledge of regulation of PML under normal cellular conditions as well as the role for regulation of PML in viral infection and cancer...
  50. Dellaire G, Ching R, Dehghani H, Ren Y, Bazett Jones D. The number of PML nuclear bodies increases in early S phase by a fission mechanism. J Cell Sci. 2006;119:1026-33 pubmed
  51. Chen Y, Kappel C, Beaudouin J, Eils R, Spector D. Live cell dynamics of promyelocytic leukemia nuclear bodies upon entry into and exit from mitosis. Mol Biol Cell. 2008;19:3147-62 pubmed publisher
    ..However, the recruitment of these proteins to PML NBs was delayed and correlated with the timing of de novo PML NB formation. Together, these results provide insight into the dynamic changes associated with PML NBs during mitosis...
  52. Villagra N, Navascues J, Casafont I, Val Bernal J, Lafarga M, Berciano M. The PML-nuclear inclusion of human supraoptic neurons: a new compartment with SUMO-1- and ubiquitin-proteasome-associated domains. Neurobiol Dis. 2006;21:181-93 pubmed
  53. Rodriguez Lebron E, Denovan Wright E, Nash K, Lewin A, Mandel R. Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice. Mol Ther. 2005;12:618-33 pubmed
    ..These results suggest that a reduction in the levels of striatal mHtt can ameliorate the HD phenotype of R6/1 mice...