The PEA-15 protein regulates autophagy via activation of JNK

• Verfasst von: Böck, Barbara [VerfasserIn]
• Verfasst von: Tagscherer, Katrin [VerfasserIn]
• Verfasst von: Faßl, Anne [VerfasserIn]
• Verfasst von: Krämer, Anika [VerfasserIn]
• Verfasst von: Oehme, Ina [VerfasserIn]
• Verfasst von: Zentgraf, Hanswalter [VerfasserIn]
• Verfasst von: Keith, Martina [VerfasserIn]
• Verfasst von: Roth, Wilfried [VerfasserIn]
• Titel: The PEA-15 protein regulates autophagy via activation of JNK
• Verf.angabe: Barbara C. Böck, Katrin E. Tagscherer, Anne Fassl, Anika Krämer, Ina Oehme, Hans-Walter Zentgraf, Martina Keith, Wilfried Roth
• E-Jahr: 2010
• Jahr: 7 May 2010
• Umfang: 11 S.
• Fussnoten: Gesehen am 26.01.2023
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2010
• Band/Heft Quelle: 285(2010), 28, Seite 21644-21654
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M109.096628
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Apoptosis
• Sach-SW: Autophagy
• Sach-SW: Brain
• Sach-SW: Brain Tumors
• Sach-SW: c-Jun N-terminal Kinase
• Sach-SW: Cell Death
• Sach-SW: JNK
• Sach-SW: PEA-15
• K10plus-PPN: 1832484564

Abstract

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.