Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis*
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CCAAT-Enhancer-Binding Proteins*
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Cell Line
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Cloning, Molecular
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Cricetinae
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DNA Damage
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DNA-Binding Proteins / biosynthesis*
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Genes, bcl-2
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Isopropyl Thiogalactoside / pharmacology
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Kinetics
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Leukemia, Myeloid, Acute
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Mice
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Mutagenesis, Site-Directed
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Nuclear Proteins / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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RNA, Messenger / biosynthesis
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Recombinant Proteins / biosynthesis
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Transcription Factor CHOP
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Transcription Factors / biosynthesis*
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Transcription, Genetic / drug effects
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / metabolism
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Ddit3 protein, mouse
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Nuclear Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Recombinant Proteins
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Transcription Factors
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Tumor Suppressor Protein p53
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Transcription Factor CHOP
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Isopropyl Thiogalactoside