Suppression of Bcl-xL deamidation in human hepatocellular carcinomas.
Bcl-xL is an antiapoptotic member of the Bcl-2 family, which inhibits apoptosis initiated by various cellular stresses, and has a pivotal role in the survival of tumor cells. Researchers have previously observed elevated expression of Bcl-xL in some human malignancies. In this study, we present evidence that human Bcl-xL is deamidated at asparagines 52 and 66 and that the rate of Bcl-xL deamidation is significantly lower in hepatocellular carcinomas than in normal or adjacent nontumor liver tissues. Because protein deamidation of Bcl-xL imports a complete "loss of function" of this antiapoptotic molecule, the present study indicates that tumor cells may acquire resistance to apoptosis and a survival advantage by suppressing deamidation as well as by increasing the expression of Bcl-xL. Thus, suppression of Bcl-xL deamidation may play a critical role in the regulation of cell death by apoptosis.
Takehara
Tetsuo
T
Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Takahashi
Hiroshi
H
D000577:Amides / Q000378:metabolism*; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D003062:Codon; D015925:Cryopreservation; D004591:Electrophoresis, Polyacrylamide Gel; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D026581:Isoaspartic Acid / Q000032:analysis*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D051020:bcl-X Protein
D000577:Amides; C494811:BCL2L1 protein, human; D003062:Codon; D026581:Isoaspartic Acid; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein