bfl-1, a bcl-2 homologue, suppresses p53-induced apoptosis and exhibits potent cooperative transforming activity.
The bcl-2 family of genes code for proteins that contain anti-apoptotic or pro-apoptotic activity. The human bfl-1 gene contains an open reading frame for a 175-amino acid Bcl-2 family protein. Among the various Bcl-2 family members, the Bfl-1 protein shares the highest homology with the mouse A1 protein. These two proteins share three conserved domains, Bcl homology (BH)1, BH2, and BH3, with other Bcl-2 family proteins. Unlike other Bcl-2 family members, Bfl-1 contains a GIn-rich NH2-terminal region and lacks an NH (19K homology) domain 1. We demonstrate that the Bfl-1 protein suppresses apoptosis induced by the p53 tumor suppressor protein in a manner similar to other Bcl-2 family members such as Bcl-2, Bcl-xL and EBV-BHRF1. In addition, the bfl-I gene cooperates efficiently with the Ela oncogene in transformation of primary rodent epithelial cells. Our results suggest that the human bfl-1 gene may play an important role in carcinogenesis.
D'Sa-Eipper
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Institute for Molecular Virology, St. Louis University Health Sciences Center, Missouri 63110, USA.
Subramanian
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Chinnadurai
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D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D051020:bcl-X Protein
D017501:Adenovirus E1B Proteins; C096816:BCL2-related protein A1; C494811:BCL2L1 protein, human; C083278:BHRF1 protein, Human herpesvirus 4; C494813:Bcl2l1 protein, rat; D015778:Minor Histocompatibility Antigens; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D051020:bcl-X Protein