The PEA-15 protein regulates autophagy via activation of JNK
PEA-15/PED (phosphoprotein enriched in astrocytes 15 kDa/phosphoprotein enriched in diabetes) is a death effector domain-containing protein which is known to modulate apoptotic cell death. The mechanism by which PEA-15 inhibits caspase activation and increases ERK (extracellular-regulated kinase) ac...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
7 May 2010
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| In: |
The journal of biological chemistry
Year: 2010, Jahrgang: 285, Heft: 28, Pages: 21644-21654 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M109.096628 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M109.096628 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0021925820601922 
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| Verfasserangaben: | Barbara C. Böck, Katrin E. Tagscherer, Anne Fassl, Anika Krämer, Ina Oehme, Hans-Walter Zentgraf, Martina Keith, Wilfried Roth |
| Zusammenfassung: | PEA-15/PED (phosphoprotein enriched in astrocytes 15 kDa/phosphoprotein enriched in diabetes) is a death effector domain-containing protein which is known to modulate apoptotic cell death. The mechanism by which PEA-15 inhibits caspase activation and increases ERK (extracellular-regulated kinase) activity is well characterized. Here, we demonstrate that PEA-15 is not only pivotal in the activation of the ERK pathway but also modulates JNK (c-Jun N-terminal kinase) signaling. Upon overexpression of PEA-15 in malignant glioma cells, JNK is potently activated. The PEA-15-induced JNK activation depends on the phosphorylation of PEA-15 at both phosphorylation sites (serine 104 and serine 116). The activation of JNK is substantially inhibited by siRNA-mediated down-regulation of endogenous PEA-15. Moreover, we demonstrate that glioma cells overexpressing PEA-15 show increased signs of autophagy in response to classical autophagic stimuli such as ionizing irradiation, serum deprivation, or rapamycin treatment. In contrast, the non-phosphorylatable mutants of PEA-15 are not capable of promoting autophagy. The inhibition of JNK abrogates the PEA-15-mediated increase in autophagy. In conclusion, our data show that PEA-15 promotes autophagy in glioma cells in a JNK-dependent manner. This might render glioma cells more resistant to adverse stimuli such as starvation or ionizing irradiation. |
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| Beschreibung: | Gesehen am 26.01.2023 |
| Beschreibung: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M109.096628 |