Three-dimensional organization of promyelocytic leukemia nuclear bodies

J Cell Sci. 2010 Feb 1;123(Pt 3):392-400. doi: 10.1242/jcs.053496.

Abstract

Promyelocytic leukemia nuclear bodies (PML-NBs) are mobile subnuclear organelles formed by PML and Sp100 protein. They have been reported to have a role in transcription, DNA replication and repair, telomere lengthening, cell cycle control and tumor suppression. We have conducted high-resolution 4Pi fluorescence laser-scanning microscopy studies complemented with correlative electron microscopy and investigations of the accessibility of the PML-NB subcompartment. During interphase PML-NBs adopt a spherical organization characterized by the assembly of PML and Sp100 proteins into patches within a 50- to 100-nm-thick shell. This spherical shell of PML and Sp100 imposes little constraint to the exchange of components between the PML-NB interior and the nucleoplasm. Post-translational SUMO modifications, telomere repeats and heterochromatin protein 1 were found to localize in characteristic patterns with respect to PML and Sp100. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear / metabolism
  • Antigens, Nuclear / ultrastructure
  • Autoantigens / metabolism
  • Autoantigens / ultrastructure
  • Cell Line, Tumor
  • HeLa Cells
  • Humans
  • Intranuclear Inclusion Bodies / metabolism*
  • Intranuclear Inclusion Bodies / ultrastructure
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Models, Biological
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / ultrastructure
  • Promyelocytic Leukemia Protein
  • SUMO-1 Protein / metabolism
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Transcription Factors / metabolism*
  • Transcription Factors / ultrastructure
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / ultrastructure
  • Ubiquitins / metabolism

Substances

  • Antigens, Nuclear
  • Autoantigens
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • SUMO-1 Protein
  • SUMO2 protein, human
  • SUMO3 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitins
  • Sp100 protein, human
  • PML protein, human