Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cells.
Bcl-2 is an intracellular membrane-associated protein that functions to block programmed cell death. Despite recurrent exposure to cellular toxins from the circulation and tissue, endothelial cells are remarkably resistant to cell death. Because Bcl-2 protein levels are low or undetectable in endothelial cells, we postulated that other members of the growing Bcl-2 family would be present in endothelial cells to provide protection against apoptosis. Degenerate primers to two conserved regions of the Bcl-2 family were used to amplify potential homologues in endothelial cells. This strategy resulted in the isolation of a human Bcl-2 homologue related to murine Al, a recently identified member of this family. We show here that, in endothelial cells, human Al is rapidly inducible by phorbol ester and the inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, but not by the growth factors, basic fibroblast growth factor or vascular endothelial growth factor. Al is the only known Bcl-2 family member that is inducible by inflammatory cytokines, suggesting that it may play a protective role during inflammation. Additionally, vascular smooth muscle cells and various nonhematopoietic tissues express human Al, indicating that human Al is a widely expressed Bcl-2 homologue.
Karsan
A
A
Department of Medicine, Division of Hematology, University of Washington, Seattle, 98195, USA.
Yee
E
E
Kaushansky
K
K
Harlan
J M
JM
D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D003001:Cloning, Molecular; D016207:Cytokines / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes; D018398:Homeodomain Proteins; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology*; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C096816:BCL2-related protein A1; D016207:Cytokines; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D018398:Homeodomain Proteins; D008222:Lymphokines; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D051818:Replication Protein C; D013755:Tetradecanoylphorbol Acetate