Phosphorylation of Smac by JNK3 attenuates its interaction with XIAP
| Autor: | Kyu Dong Yoo, Seung Ki Lee, Byoung Duck Park, Seung-Ju Cho, Hyun Ji Jeong, Young Mi Ham, Young Tae Je |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Poly ADP ribose polymerase
Biophysics Apoptosis X-Linked Inhibitor of Apoptosis Protein Inhibitor of apoptosis Biochemistry HeLa Mitochondrial Proteins Mitogen-Activated Protein Kinase 10 medicine Humans Mitogen-Activated Protein Kinase 8 Phosphorylation Molecular Biology Etoposide biology Chemistry Intracellular Signaling Peptides and Proteins Cell Biology biology.organism_classification XIAP Mechanism of action Cancer research Apoptosome biological phenomena cell phenomena and immunity medicine.symptom Apoptosis Regulatory Proteins HeLa Cells |
| Zdroj: | Biochemical and biophysical research communications. 361(4) |
| ISSN: | 0006-291X |
| Popis: | Here we demonstrate that JNK3 can phosphorylate Smac. Smac phosphorylation attenuates its ability to activate apoptosome activity in HeLa S-100 cell lysates. Addition of the X-linked inhibitor of apoptosis protein (XIAP) to the S-100 markedly suppresses apoptosome activity, and this suppressive effect of XIAP is neutralized by adding unphosphorylated Smac, but not phosphorylated Smac. Furtherover, JNK3-mediated phosphorylation of Smac markedly attenuates the interaction between Smac and XIAP, as measured by BIACORE assays and non-denaturing gel shift assays. When JNK3 activity is down-regulated in etoposide-induced HeLa cells by transiently overexpressing a dominant negative version of JNK3 (DN-JNK3), the caspase-3 activity as well as PARP cleavages are markedly enhanced. And the interaction of Smac with XIAP also increases by down-regulating JNK3 activity under the same conditions. These results suggest that JNK3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between Smac and XIAP. |
| Databáze: | OpenAIRE |
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