Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 and 25 differently
| Autor: | Alexander M. Ishov, Jennifer S. Michaelson, Dmitri Negorev, Gerd G. Maul, Robert M. Tanguay, Isabelle Nefkens, Edward T.H. Yeh, Werner E.G. Müller |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Co-Repressor Proteins
MAP Kinase Signaling System Macromolecular Substances SUMO-1 Protein Promyelocytic Leukemia Protein Mice Promyelocytic leukemia protein Death-associated protein 6 Stress Physiological Heat shock protein Endopeptidases Animals HSP70 Heat-Shock Proteins Enzyme Inhibitors Heat shock Transcription factor Cells Cultured Heat-Shock Proteins biology Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins Nuclear Proteins Cell Biology Cell Nucleus Structures Neoplasm Proteins Cell biology Hsp70 Cysteine Endopeptidases Eukaryotic Cells Gene Expression Regulation Immunology biology.protein Signal transduction Carrier Proteins Heat-Shock Response Cadmium Molecular Chaperones Transcription Factors |
| Zdroj: | Journal of Cell Science. 116:513-524 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.00253 |
| Popis: | Nuclear domains called ND10 or PML bodies might function as nuclear depots by recruiting or releasing certain proteins. Although recruitment of proteins through interferon-induced upregulation and SUMO-1 modification level of PML had been defined, it is not known whether release of proteins is regulated and has physiological consequences. Exposure to sublethal environmental stress revealed a sequential release of ND10-associated proteins. Upon heat shock Daxx and Sp100 were released but PML remained, whereas exposure to subtoxic concentrations of CdCl2 induced the release of ND10-associated proteins, including PML, with Sp100 remaining in a few sites. In both cases,recovery times were similar and were followed by a burst of mitotic activity. Cadmium-induced release of proteins from ND10 could be blocked by inhibiting activation of p38 MAPK or ERK1/2. By contrast, heat-shock-induced desumolation of PML and release of proteins from ND10 are unaffected by these inhibitors but can be recapitulated by overexpression of the SUMO isopeptidase SENP-1. Therefore, activation of SENP-1-like SUMO isopeptidase(s) during heat shock is not affected by these kinases. Thus, the release of ND10-associated proteins is not due to a general dispersal of nuclear domains but seems to be regulated by rapid desumolation during thermal stress and through the phosphorylation cascade of stress and mitogenic signaling pathways in the case of CdCl2. Whether the release of certain proteins had consequences was tested for heat-shock-protein transcription and synthesis. Release of Daxx correlated with Hsp25 suppression, suggesting that Daxx normally inhibits immediate Hsp25 production. Release of PML correlated with lower production of Hsp70. These results suggest that segregation or release of PML or Daxx have differential physiological relevance during the stress response. The fact that enzymatic activation of protein release or segregation after stress modifies the heat-shock response strengthens the concept of ND10 as a regulated depot of effector proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|