PML nuclear bodies in the pathogenesis of
نویسندگان
چکیده
1. Abstract 2. Introduction 2.1. The PML gene 2.2. PML nuclear bodies (PML-NBs) 3. PML-NB disruption and acute promyelocytic leukemia (APL) 3.1. t (15;17) associated APL and PML-NB disruption 3.2. Alternative APL Fusions 3.3. Homodimerization of the APL fusion proteins 3.4. Is forced dimerization of RARA and transcriptional repression sufficient for leukemogenesis? 4. Evidence supporting PML-NB disruption as an “active player” in leukemogenesis 4.1. PML-NBs, tumor suppression and cancer 4.2. Further evidence supporting a role for the PML protein in the pathogenesis of APL 4.3. How does PML-NB disruption affect their constituent proteins and what are the possible downstream consequences? 4.3.1. Myeloid differentiation 4.3.2. RNA processing and translation 4.3.3. Intracellular proteolysis 4.3.4. Post-translational modifications of proteins 4.3.5. Apoptosis 4.3.6. Genome stability 4.3.7. Gene transcription 5. PML-NB disruption may be an “innocent bystander” effect in APL 5.1. Lack of PML-NB disruption in the alternative APL fusions 5.2. PML-NB formation is not required for PML induced premature senescence 5.3. Lack of a major impact of PML-NB disruption on gene expression profiles 5.4. The role of cytoplasmic PML 5.5. PML-NB functions: “guilt by association” 5.6. Apoptosis 6. Perspective: Is PML-NB disruption an “active player” or” innocent bystander” in the pathogenesis of APL? 7. Acknowledgements 8. References
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