[PML isoforms and TGF-β response]

PML/TRIM19 is the organizer of PML nuclear bodies (NB), a multiprotein complex associated to the nuclear matrix, which recruit a large number of proteins involved in various cellular processes. Alternative splicing from a single PML gene generates 6 nuclear PML isoforms (PMLI to PMLVI) and one cytoplasmic isoform, PMLVII. Murine PML-null primary cells are resistant to TGF-β-induced apoptosis. Cytoplasmic PML is an essential activator of TGF-β signaling by increasing the phosphorylation of transcription factors SMAD2/3 while nuclear PML plays a role in TGF-β-induced caspase 8 activation and apoptosis. TGF-β targets nuclear PML by inducing its conjugation to SUMO. In the nucleus, PML is mainly expressed in the nucleoplasm with a small fraction in the nuclear matrix. In response to TGF-β, PML and caspase 8 shift to the nuclear matrix, where both PML and caspase 8 colocalise within PML NBs. Here, we review the implication of cytoplasmic and nuclear PML isoforms in TGF-β response.