Identification of ADP-ribosylation factor 4 as a suppressor of N-(4-hydroxyphenyl)retinamide-induced cell death.
Yeast-based functional screening for inhibitors of Bcl-2-associated X protein (Bax)-induced cell death in yeast identified ADP-ribosylation factor 4 (ARF4) as a novel anti-apoptotic gene in human glioblastoma-derived U373MG cells. Yeast or U373MG cells that overexpressed ARF4 exhibited reduced reactive oxygen species (ROS) generation in response to Bax or N-(4-hydroxyphenyl)retinamide (4-HPR), respectively, which suggests that ROS play a role in the inhibition of cell death by ARF4. The 4-HPR-mediated phosphorylation of c-JUN N-terminal kinase, p38, and extracellular signal-regulated kinase was markedly suppressed in U373MG cells that stably expressed ARF4. Stable ARF4 transfectants were also refractory to 4-HPR-induced mitochondrial translocation of Bax, release of mitochondrial cytochrome c, and activation of caspase-3. Our results suggest that ARF4 participates in the regulation of glioblastoma apoptosis through the inhibition of stress-mediated apoptotic signals.
Woo
Im Sun
IS
Department of Pharmacology, Gyeongsang Institute of Health Science, Gyeongsang National University School of Medicine, 92 Chilam-dong, Jinju 660-751, Republic of Korea.
Eun
So Young
SY
Jang
Han-Su
HS
Kang
Eun Sil
ES
Kim
Gil Hyeong
GH
Kim
Hye Jung
HJ
Lee
Jae Heun
JH
Chang
Ki Churl
KC
Kim
Jin-Hoi
JH
Han
Chang Woo
CW
Seo
Han Geuk
HG
D020727:ADP-Ribosylation Factors / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017313:Fenretinide / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression; D015723:Gene Library; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D017313:Fenretinide; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020727:ADP-Ribosylation Factors; C116688:ARF4 protein, human