PML nuclear bodies

Abstract

PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these domains drew instant interest onto them. The multiple levels of PML body regulation by a specific posttranslational modification, sumoylation, have raised several unsolved issues. Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma.

Figure 1.

Different types of PML bodies. Immuno-gold electron microscopy of PML NBs in CHO cell line stably overexpressing PML. (A, B, C) “Classical” PML NBs. PML is distributed on a dense electron shell (A, B) or on light halo (C), that can contain a microgranular inner core (B, C) or not (A). (D, E) PML body in arsenic trioxide-treated cell. Note the absence of the inner core and the enrolled fibrillar aspect of the body (D). (F) PML-II targets the inner membrane region of the nuclear envelope in pml-/- MEF cells. Images courtesy of Edmond and Francine Puvion (CNRS, Villejuif, France).

Figure 2.

Schematic representation of PML NB biogenesis. PML proteins first dimerize through the RBCC domains and then multimerize to nucleate NBs. PML sumoylation then leads to organization in spherical body. SIM-containing or sumoylated partners (or both) are recruited by the SUMO or SIM of PML into the inner core of the body.

Figure 3.

A general function for PML NBs: Integrated posttranslational protein modifications? PML NBs regulate posttranslational modifications of partner proteins like sumoylation, ubiquitination, but also phosphorylation or acetylation. These modifications regulate a wide variety of partners, leading to modulation of biological processes like transcription, apoptosis/senescence, DNA repair, or ALT and stem cell self-renewal.