A novel 52 kDa protein induces apoptosis and concurrently activates c-Jun N-terminal kinase 1 (JNK1) in mouse C3H10T1/2 fibroblasts.
A 52 kDa protein (p52) was purified from chicken embryos and its corresponding cDNA was cloned. The p52 cDNA is 1768 bp long and has an open reading frame of 465 amino acids. The sequence of the p52 cDNA shows significant homology with mouse and human cDNAs from the EST database, so do the deduced amino acid sequences, indicating the existence of human and mouse homologues of p52. Northern blot hybridization showed that the p52 mRNA was expressed in a wide range of embryonic and adult tissues. There was more p52 mRNA in embryonic heart and liver than in the brain or muscle. The adult testis had the highest level of p52 mRNA, whereas adult liver had the lowest. Expression of p52 in mouse C3H10T1/2 fibroblasts caused apoptotic cell death, upregulation of transcription factor c-Jun and activation of c-Jun N-terminal kinase 1 (JNK1). In addition, expression of Bcl-2, but not of the dominant negative mutant JNK1, can block the p52-mediated apoptosis. These results indicate that p52 may represent a new cell-death protein inducing apoptosis and activating JNK1 through different pathways.
Sun
L
L
Friedrich Miescher Institute, Basel, Switzerland.
Liu
Y
Y
Frémont
M
M
Schwarz
S
S
Siegmann
M
M
Matthies
R
R
Jost
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002642:Chick Embryo; D018076:DNA, Complementary; D004789:Enzyme Activation; D005347:Fibroblasts; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013737:Testis / Q000378:metabolism; D014162:Transfection
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D011994:Recombinant Proteins; C111664:protein p52, mammalian; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases