PML nuclear bodies and apoptosis

Abstract

Promyelocytic leukaemia nuclear bodies (PML NBs) are structured protein complexes associated with the nuclear matrix. PML constitutes the scaffold component of NBs and recruits onto these domains a striking variety of proteins, many of which are involved in apoptosis control. Several reports have directly implicated PML in apoptosis and senescence, but the mechanisms by which these are conveyed are still largely unsettled. Recruitment of partner proteins onto NBs is regulated by PML sumolation, a specific post-translational modification also found in many NB-associated proteins. Among these, several are implicated in transcription repression or activation, like the transcriptional repressor Daxx or the transcriptional activator P53. Whether NBs constitute platforms where active sites of enzymatic modifications are carried out, as suggested for P53, sites of intranuclear protein sequestration, as proposed for Daxx or organelles specialized in catabolism, is still debated. A variety of stress-related signalling pathways dramatically modulate the formation of PML NBs, which may provide a clue as to their physiological function.