[Frontiers in Bioscience 14, 1182-1196, January 1, 2009]

PML nuclear bodies and their spatial relationships in the mammalian cell nucleus

Elizabeth Batty, Kirsten Jensen, Paul Freemont

Macromolecular Structure and Function Lab, Division of Molecular Biosciences, Imperial College London, Biochemistry Building, South Kensington Campus, London, SW7 2AZ, U.K.

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. The mammalian nucleus and functional compartmentalization
2.2. PML nuclear bodies
2.2.1. PML nuclear body composition
2.2.2. PML gene locus and PML isoforms
2.2.3. PML NB formation
2.2.4. Functions of PML NBs
3. Spatial relationships in the mammalian nucleus
3.1. Spatial organization of the nucleus - possible driving mechanisms
3.2. Types of spatial relationships and associations in the nucleus
3.2.1. Complete co-localization
3.2.1.1. Sp100
3.2.1.2. CBP
3.2.1.3. SATB1 (MAR-binding protein)
3.2.1.4. eIF4E
3.2.1.5. PLZF
3.2.2. Partial co-localization
3.2.2.1. Cajal bodies
3.2.2.2. Active transcriptional domains
3.2.2.3. Proteasomal protein degradation
3.2.2.4. Telomeres
3.2.3. Adjacent co-localization
3.2.3.1. Middle-late S-phase replication domains
3.2.3.2. PLC-gamma 1
3.2.3.3. Chromosome territories
3.2.3.4. Splicing speckles
3.2.4. Induced relationships with PML NBs
3.2.4.1. DNA damage
3.2.4.1.1. Single strand DNA damage
3.2.4.1.2. Double strand DNA damage
3.2.4.2. Viral infection and response to foreign DNA
3.2.4.2.1. Viral infection
3.2.4.2.2. Foreign DNA
3.2.4.3. The Interferon response
3.2.4.3.1. NDH II
3.2.4.3.2. PA28 and the immunoproteasome
3.2.4.4. Stress
3.2.4.4.1. Stress and nucleoli
3.2.4.4.2. Proteasomal inhibition and centromeres
3.2.5. Associations with PML NBs to a varying degree
3.2.5.1. MHC
4. What affects PML NB spatial relationships and associations?
4.1. Cell-related factors
4.1.1. Cell-line specific factors and disease states
4.1.2. PML cell cycle dynamics - protein expression, NB number and size
4.1.3. PML NB movement and dynamics
4.1.4. PML isoforms
4.2. Method-related factors
4.2.1. Fixation, permeabilization and immunofluorescence
4.2.2. Imaging methods
4.2.3. Choice of experimental time points
4.2.4. Effects of stress and handling of cells upon PML NBs
4.2.5. Over-expression of transiently and stably transfected PML
5. How do we measure PML NB - nuclear compartment relationships?
6. Perspective
7. Acknowledgements
8. References

1. ABSTRACT

Promyelocytic leukaemia nuclear bodies (PML NBs) are found within the nucleus of mammalian cells, and are formed from the constituent proteins PML and Sp100. Numbering between 10 and 30 per cell, they are an obvious feature of the nuclear landscape, yet their functions have still to be unambiguously defined. In the mammalian nucleus, compartmentalization of functions is apparent, as reflected in the wide-range of other nuclear compartments that can be identified. These include nucleoli, transcription foci, splicing speckles, chromosomal topological markers such as centromeres and telomeres, the nuclear boundary, and the nucleoplasm itself. Quantification of the otherwise qualitative observations of relationships between mammalian nuclear compartments is essential for a complete understanding of nuclear processes. Here we describe some of the interesting known associations between PML NBs and other nuclear compartments, and comment upon their implications for PML NB function.