Induction of Bax protein and degradation of lamin A during p53-dependent apoptosis induced by chemotherapeutic agents in human cancer cell lines.
In this study, subcellular fractionation analysis was performed to investigate the intracellular localization of Bax protein. We demonstrated that Bax protein is localized primarily in the nuclear and heavy membrane fractions. The expression of Bax protein in the nuclear membrane was induced in wild-type p53 human cancer cells (COLO 205 and Hep G2) by a wide variety of cancer chemotherapeutic agents in order to scrutinize further the biologic function of the Bax protein in the nuclear membrane. We found that lamin A and poly-(ADP ribose) polymerase (PARP) protein degradation coincided when the Bax protein level was elevated in the nuclear membrane of cells affected by drug stimuli. By using anti-sense oligodeoxynucleotides specific to human Bax mRNA, we further demonstrated that inhibition of Bax expression could specifically block lamin A but not PARP cleavage in apoptotic cancer cells.
Ho
Y S
YS
School of Medical Technology, Taipei Medical College, Taiwan, Republic of China.
Lee
H M
HM
Chang
C R
CR
Lin
J K
JK
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D016158:Genes, p53; D006801:Humans; D034904:Lamin Type A; D034882:Lamins; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases