Cap-independent protein translation is initially responsible for 4-(N-methylnitrosamino)-1-(3-pyridyl)-butanone (NNK)-induced apoptosis in normal human bronchial epithelial cells.
Evidences show that eukaryotic mRNAs can perform protein translation through internal ribosome entry sites (IRES). 5'-Untranslated region of the mRNA encoding apoptotic protease-activating factor 1 (Apaf-1) contains IRES, and, thus, can be translated in a cap-independent manner. Effects of changes in protein translation pattern through rapamycin pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-butanone(NNK, tobacco-specific lung carcinogen)-induced apoptosis in human bronchial epithelial cells were examined by caspase assay, FACS analysis, Western blotting, and transient transfection. Results showed that NNK induced apoptosis in concentration- and time-dependent manners. NNK-induced apoptosis occurred initially through cap-independent protein translation, which during later stage was replaced by cap-dependent protein translation. Our data may be applicable as the mechanical basis of lung cancer treatment.
Moon
Seo-Hyun
SH
Lab of Toxicology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea.
Kim
Hyun-Woo
HW
Kim
Jun-Sung
JS
Park
Jin-Hong
JH
Kim
Hwa
H
Eu
Gook-Jong
GJ
Cho
Hyun-Sun
HS
Kang
Ga-Mi
GM
Lee
Kee-Ho
KH
Cho
Myung-Haing
MH
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1; D051023:BH3 Interacting Domain Death Agonist Protein; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D002273:Carcinogens / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D009602:Nitrosamines / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D039381:RNA Cap-Binding Proteins / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors; D051028:bcl-2-Associated X Protein
C506592:APAF1 protein, human; D000903:Antibiotics, Antineoplastic; D053477:Apoptotic Protease-Activating Factor 1; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002273:Carcinogens; D002352:Carrier Proteins; D039561:Eukaryotic Initiation Factor-4E; D009602:Nitrosamines; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D039381:RNA Cap-Binding Proteins; D051028:bcl-2-Associated X Protein; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D045304:Cytochromes c; D020169:Caspases; D020123:Sirolimus