Body language: the function of PML nuclear bodies in apoptosis regulation.
Promyelocytic leukaemia (PML) nuclear bodies (NBs) are macromolecular nuclear domains present in virtually every mammalian cell. PML nuclear bodies (PML-NBs) were functionally linked to various fundamental cellular processes, including transcriptional control, tumour suppression and apoptosis regulation. Supporting the important function of PML and its associated NBs in apoptosis regulation, several apoptotic regulators localise to PML-NBs, and cells from PML-deficient mice show severe apoptotic defects, including induction of genotoxic stress and death receptor CD95 (Fas/APO-1) activation. Based on the current literature, we hypothesise that PML-NBs regulate apoptosis through different molecular mechanisms, on the one hand by acting as macromolecular scaffolds for recruitment and post-translational modification of the apoptotic key regulator p53, and on the other by regulating the subcellular bioavailability and quality of some apoptotic signal transducers.
Hofmann
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1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistrasse 52, Hamburg 20251, Germany. thomas.hofmann@hpi.uni-hamburg.de
Will
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D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D000071156:Promyelocytic Leukemia Protein; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D019014:fas Receptor / Q000378:metabolism
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019014:fas Receptor