Thymidine phosphorylase suppresses Fas-induced apoptotic signal transduction independent of its enzymatic activity.
Thymidine phosphorylase (TP) has chemotactic and angiogenic activities resulting from its enzymatic activity in vitro, and it also promotes tumor growth and inhibits apoptosis in vivo. Recently, we have reported that TP plays an important role in Fas-induced apoptosis. Caspase-8 cleavage, subsequent cytochrome c release, and caspase-3 cleavage were prevented in KB cells transfected with a TP cDNA (KB/TP cells). In this study, treatment with thymidine phosphorylase inhibitor (TPI) or thymidine did not affect cell survival of KB/TP cells during Fas-induced apoptosis. Moreover, treatment with thymine or 2-deoxy-D-ribose (degradation products of thymidine generated by TP) also did not affect cell survival of control transfectant (KB/CV) cells during Fas-induced apoptosis. These findings indicate that TP suppresses Fas-induced apoptotic signal transduction independent of its enzymatic activity.
Mori
Shin-ichiro
S
First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890, Japan. morishin@m3.kufm.kagoshima-u.ac.jp
Takao
Sonshin
S
Ikeda
Ryuji
R
Noma
Hidetoshi
H
Mataki
Yuko
Y
Wang
Xin
X
Akiyama
Shin-ichi
S
Aikou
Takashi
T
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D003855:Deoxyribose / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D015398:Signal Transduction / Q000502:physiology*; D013936:Thymidine / Q000494:pharmacology; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors / Q000502:physiology*; D013941:Thymine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D019014:fas Receptor; D003855:Deoxyribose; D013939:Thymidine Phosphorylase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013941:Thymine; D013936:Thymidine