bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death

Cell. 1993 Aug 27;74(4):597-608. doi: 10.1016/0092-8674(93)90508-n.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Cell Line
  • Cell Survival / genetics
  • Chickens
  • Cloning, Molecular
  • Genes, Dominant
  • Genes, Regulator*
  • Humans
  • Interleukin-3 / pharmacology
  • Kinetics
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Transfection
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • Interleukin-3
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-X Protein
  • Protein-Tyrosine Kinases

Associated data

  • GENBANK/L14569
  • GENBANK/L20120
  • GENBANK/L20121
  • GENBANK/L20122
  • GENBANK/L33709
  • GENBANK/S60902
  • GENBANK/S60903
  • GENBANK/S60904
  • GENBANK/S60905
  • GENBANK/S60924
  • GENBANK/Z23110
  • GENBANK/Z23115
  • GENBANK/Z23116