Importance of the Bcl-2 family in cell death regulation.
Bcl-2 was first identified as a novel transcript associated with the t(14;18) chromosomal breakpoint which occurs in most follicular lymphomas. The deregulated expression of bcl-2 was found to contribute to multistep neoplasia through the suppression of cell death, or apoptosis, in transgenic mouse models. Bcl-2 was subsequently shown to be normally expressed in a variety of tissues and to significantly inhibit the induction of apoptosis in many experimental systems. Bcl-2 is now known to be structurally similar to other proteins, in particular within the domains referred to as BH1 and BH2. This multigene family of cell death regulators includes members which enhance rates of apoptosis, including bcl-xs and bax, and those which inhibit apoptosis, including MCL-1 and bcl-xL. Members of the bcl-2 family physically interact with other proteins, including other family members and these interactions appear to modulate their function. The mechanism(s) by which bcl-2 family members regulate cell death remain in large part unknown, although recent evidence suggests that bcl-2 may interfere with cellular signalling events involved in apoptosis induction.
McDonnell
T J
TJ
Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Beham
A
A
Sarkiss
M
M
Andersen
M M
MM
Lo
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P
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000502:physiology; D016923:Cell Death; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494819:BAD protein, human; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494820:Bad protein, mouse; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; C494812:Bcl2l1 protein, mouse; D002352:Carrier Proteins; C579094:Mcl1 protein, mouse; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein