bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death.
We report the isolation of bcl-x, a bcl-2-related gene that can function as a bcl-2-independent regulator of programmed cell death (apoptosis). Alternative splicing results in two distinct bcl-x mRNAs. The protein product of the larger mRNA, bcl-xL, is similar in size and predicted structure to Bcl-2. When stably transfected into an IL-3-dependent cell line, bcl-xL inhibits cell death upon growth factor withdrawal at least as well as bcl-2. Surprisingly, the second mRNA species, bcl-xS, encodes a protein that inhibits the ability of bcl-2 to enhance the survival of growth factor-deprived cells. In vivo, bcl-xS mRNA is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, bcl-xL is found in tissues containing long-lived postmitotic cells, such as adult brain. Together these data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death.
Boise
L H
LH
Howard Hughes Medical Institute, Department of Medicine, University of Chicago, Illinois 60637.
González-García
M
M
Postema
C E
CE
Ding
L
L
Lindsten
T
T
Turka
L A
LA
Mao
X
X
Nuñez
G
G
Thompson
C B
CB
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D002645:Chickens; D003001:Cloning, Molecular; D005799:Genes, Dominant; D005809:Genes, Regulator; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D007377:Interleukin-3; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D011505:Protein-Tyrosine Kinases