ASK1-JNK signaling cascade mediates Ad-ST13-induced apoptosis in colorectal HCT116 cells.
ST13, a co-factor of heat shock protein, has shown potential antitumor efficacy for colorectal cancer in our previous study. However, the molecular mechanisms governing ST13-induced apoptosis are poorly understood. Here, we demonstrate that Ad-ST13 (ST13 mediated by adenovirus) activates apoptosis signal-regulated kinase (ASK1) and c-Jun N-terminal kinase (JNK) but not p38 (mitogen-activated protein kinase) in human colorectal HCT116 cells. Ad-ST13 also increases extracellular-regulated kinase (ERK) phosphorylation levels, but the change is due to adenovirus replication. Overexpression of ST13 also increases the transcription activity of AP-1. Blocking ASK1-JNK pathway affects Ad-ST13-mediated colorectal cell apoptosis, decreases the release of cytochrome c in cytoplasm and caspase activation. Because ASK1 is known to contain a tetratricopeptide repeat (TPR)-acceptor site and ST13 has TPR domain, we found the interaction between ST13 and ASK1. These results strongly indicate Ad-ST13 triggers colorectal cell apoptosis via ASK1-JNK signaling cascade.
Yang
Min
M
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Yu
Mingcan
M
Guan
Dongyin
D
Gu
Jinfa
J
Cao
Xin
X
Wang
Weiyun
W
Zheng
Shu
S
Xu
Yingying
Y
Shen
Zonghou
Z
Liu
Xinyuan
X
D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D006801:Humans; D047468:Immunoprecipitation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D048670:MAP Kinase Kinase 4; D048848:MAP Kinase Kinase Kinase 5; D025521:Tumor Suppressor Proteins; C101119:ST13 protein, human; D018832:Molecular Chaperones; C482858:MAP3K5 protein, human