TGF-β induces PML SUMOylation, degradation and PML nuclear body disruption
| Autor: | Faten El-Asmi, Laurent Dianoux, Bouchra El-Mchichi, Mohamed Ali Maroui, Mounira K. Chelbi-Alix |
|---|---|
| Přispěvatelé: | Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
viruses [SDV]Life Sciences [q-bio] Immunology SUMO protein Apoptosis Protein degradation Promyelocytic Leukemia Protein Caspase 8 Biochemistry 03 medical and health sciences 0302 clinical medicine Interferon Transforming Growth Factor beta Cell Line Tumor medicine Immunology and Allergy Humans Nuclear Matrix Molecular Biology Cell Nucleus Nucleoplasm Chemistry Alternative splicing virus diseases Interferon-alpha Sumoylation Hematology Nuclear matrix Cell biology Enzyme Activation 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Proteolysis Small Ubiquitin-Related Modifier Proteins Ectopic expression medicine.drug Protein Binding |
| Zdroj: | Cytokine Cytokine, Elsevier, 2019, 120, pp.264-272. ⟨10.1016/j.cyto.2019.05.008⟩ |
| ISSN: | 1043-4666 1096-0023 |
| DOI: | 10.1016/j.cyto.2019.05.008⟩ |
| Popis: | ProMyelocytic Leukemia (PML) protein is essential for the formation of nuclear matrix-associated organelles named PML nuclear bodies (NBs) that act as a platform for post-translational modifications and protein degradation. PML NBs harbor transiently and permanently localized proteins and are associated with the regulation of several cellular functions including apoptosis. There are seven PML isoforms, six nuclear (PMLI-VI) and one cytoplasmic (PMLVII), which are encoded by a single gene via alternative RNA splicing. It has been reported that murine PML-null primary cells are resistant to TGF-β-induced apoptosis and that cytoplasmic PML is an essential activator of TGF-β signaling. The role and the fate of interferon (IFN)-enhanced PML NBs in response to TGF-β have not been investigated. Here we show that IFNα potentiated TGF-β-mediated apoptosis in human cells. IFNα or ectopic expression of PMLIV, but not of PMLIII, enhanced TGF-β-induced caspase 8 activation. In response to TGF-β, both PMLIII and PMLIV were conjugated to SUMO and shifted from the nucleoplasm to the nuclear matrix, however only PMLIV, via its specific C-terminal region, interacted with caspase 8 and recruited it within PML NBs. This process was followed by a caspase-dependent PML degradation and PML NB disruption. Taken together, these findings highlight the role of PML NBs in the enhancement by IFN of TGF-β-induced apoptosis and caspase 8 activation. |
| Databáze: | OpenAIRE |
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