Abnormal intracellular localization of Bax with a normal membrane anchor domain in human lung cancer cell lines.
Proapoptotic Bax is a member of the Bcl-2 family proteins, which have a key role in regulating programmed cell death. The intracellular localization and redistribution of Bax are important in promoting apoptosis. Bax contains a BH3 domain heterodimerizing with Bcl-2 and a hydrophobic transmembrane segment to be inserted in specified organelle membranes. In this study, Bcl-2 showed cytoplasmic localization in all of ten human lung cancer cell lines tested. Interestingly, Bax was localized in the nucleus in 7 cell lines, although Bax lacks nuclear import signals. This may allow cancer cells to escape from apoptosis. Why Bax is able to exist in the nucleus is still unclear. We hypothesized that mutation in the BH3 domain and / or transmembrane segment of Bax possibly causes intracellular Bax distribution. We analyzed the sequence of the bax gene in these cell lines and found only a silent point mutation at codon 184 (TCG-->TCA) in the transmembrane segment in all cell lines. This finding indicates that changes in cellular localization of Bax in lung cancer cell lines do not depend on bax mutation and that Bax is possibly translocated into the nucleus without any mutation. This is the first report showing that Bax with the normal amino acid sequence can be localized in the nucleus in established lung cancer cell lines without any treatment of the cells.
Salah-eldin
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A
Department of Environmental Medicine and Informatics, Graduate School of Environmental Earth Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan. inoues@ees.hokudai.ac.jp
Inoue
S
S
Tsuda
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M
Matsuura
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D000230:Adenocarcinoma; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D018288:Carcinoma, Small Cell; D002294:Carcinoma, Squamous Cell; D017931:DNA Primers; D019281:Dimerization; D005091:Exons; D005784:Gene Amplification; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008175:Lung Neoplasms; D009154:Mutation; D015388:Organelles / Q000378:metabolism* / Q000648:ultrastructure; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein