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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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Main Authors: Böck, Barbara (Author) , Tagscherer, Katrin (Author) , Faßl, Anne (Author) , Krämer, Anika (Author) , Oehme, Ina (Author) , Zentgraf, Hanswalter (Author) , Keith, Martina (Author) , Roth, Wilfried (Author)
Format: Article (Journal)
Language:English
Published: 7 May 2010
In: The journal of biological chemistry
Year: 2010, Volume: 285, Issue: 28, Pages: 21644-21654
ISSN:1083-351X
DOI:10.1074/jbc.M109.096628
Online Access: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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Author Notes:Barbara C. Böck, Katrin E. Tagscherer, Anne Fassl, Anika Krämer, Ina Oehme, Hans-Walter Zentgraf, Martina Keith, Wilfried Roth
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Summary: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.
Item Description:Gesehen am 26.01.2023
Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M109.096628

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