p53 mutants have selective dominant-negative effects on apoptosis but not growth arrest in human cancer cell lines.
A bidirectional expression vector that allowed equal transcription of cloned wild-type and mutant p53 cDNAs from the same vector was developed. The vector was transfected into CaLu 6 lung carcinoma cells or Saos-2 osteosarcoma cells. All p53 mutants examined were recessive to wild-type p53 transactivation of p21(WAF1/CIP1) but dominant-negative for transactivation of Bax. An examination of effects on growth arrest and apoptotic pathways indicated that all mutants were recessive to wild type for growth arrest but only three of seven mutants were dominant negative for induction of apoptosis.
Aurelio
O N
ON
Department of Microbiology, University of California-Irvine, College of Medicine, Irvine, California 92697-4025, USA.
Kong
X T
XT
Gupta
S
S
Stanbridge
E J
EJ
D017209:Apoptosis / Q000235:genetics*; D001859:Bone Neoplasms; D002289:Carcinoma, Non-Small-Cell Lung; D002455:Cell Division / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004791:Enzyme Inhibitors; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms; D012516:Osteosarcoma; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein