Bcl-X is the major pleiotropic anti-apoptotic gene activated by retroviral insertion mutagenesis in an IL-3 dependent bone marrow derived cell line.
In order to identify genes capable of inhibiting apoptosis induced by different pathways, without inducing proliferation we have performed retroviral insertion mutagenesis in the IL-3 dependent bone marrow derived Baf-3 cell line. Out of 200 mutants obtained in three separate mutagenesis experiments, four mutants were resistant to multiple apoptosis inducing pathways (including growth factor starvation, staurosporine, etoposide and cyclosporin A) and did not proliferate in the absence of IL-3. These four mutants overexpress the bcl-X gene following a retroviral insertion 5' of the translation initiation site. These results indicate that the bcl-X gene is a major pleiotropic anti-apoptotic gene in Baf-3 cells. They also suggest that the Bcl-2 family of genes might be the only one capable of inhibiting apoptosis induced by multiple pathways without inducing cell proliferation.
Thomas
J
J
Immunologie cellulaire, LBMC de L'ENS Lyon, CNRS UMR49 INRA LA 913, France.
Leverrier
Y
Y
Marvel
J
J
D000483:Alleles; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D015321:Gene Rearrangement; D007377:Interleukin-3 / Q000378:metabolism*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D016662:Virus Integration; D051020:bcl-X Protein
D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D004247:DNA