Review
Cell Death and Differentiation (2003) 10, 1290–1299, doi:10.1038/sj.cdd.4401313 Published online 22 August 2003
Body language: the function of PML nuclear bodies in apoptosis regulation
Edited by G. Mellino
1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistra
e 52, Hamburg 20251, Germany
Correspondence: TG Hofmann, Tel.: +49-40-48051322; Fax: +49-40-48051222; E-mail: thomas.hofmann@hpi.uni-hamburg.de
Received 23 May 2003; Revised 10 July 2003; Accepted 16 July 2003; Published online 22 August 2003.
Abstract
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.
Keywords:
PML nuclear body, apoptosis, CD95 (Fas/APO-1), p53, post-translational modification
Abbreviations:
AIF, apoptosis-inducing factor; APAF-1, apoptosis-activating factor 1; APL, acute promyelocytic leukaemia; ARF, alternative reading frame; As2O3, arsenic trioxide; ASK1, apoptosis signal-regulating kinase 1; ATM, ataxia-telangiectasia mutated; CBP, CREB-binding protein; DD, death domain; DED, death-effector domain; DISC, death-inducing signalling complex; HAUSP, herpesvirus-associated ubiquitin-specific protease; HIPK, homeodomain-interacting protein kinase; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; PIAS, protein inhibitor of activated STAT; PML, promyelocytic leukaemia; SAE, SUMO-1-activating enzyme; SUMO, small ubiquitin-related modifier; TGF, transforming growth factor; TNF-R, tumour necrosis factor receptor; TRADD, TNF-R1-associated death domain protein; TRAIL, tumour necrosis factor-related apoptosis-inducing ligand; UV, ultraviolet
