Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells.
CHOP (GADD153) is a member of the C/EBP family and a stress-induced protein. To investigate the role of CHOP in cellular growth, we expressed CHOP conditionally in M1 myeloblastic leukemia cells that do not express p53 protein. More than 60% of M1 cells died through apoptosis 72 h after CHOP induction. Site-directed mutagenesis revealed that this process requires leucine zipper domain but neither intact basic region nor trans-activation domain. CHOP-mediated apoptosis accompanied downregulation of bcl-2 mRNA and overexpression of Bcl-2 delayed the process. Our results indicate that CHOP can induce apoptosis in a p53-independent manner.
Matsumoto
M
M
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Minami
M
M
Takeda
K
K
Sakao
Y
Y
Akira
S
S
D000818:Animals; D017209:Apoptosis; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D019254:Genes, bcl-2; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051742:Transcription Factor CHOP; D007544:Isopropyl Thiogalactoside