A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions.
Regulation of the cell death program involves physical interactions between different members of the Bcl-2 family that either promote or suppress apoptosis. The Bcl-2 homolog, Bak, promotes apoptosis and binds anti-apoptotic family members including Bcl-2 and Bcl-xL. We have identified a domain in Bak that is both necessary and sufficient for cytotoxic activity and binding to Bcl-xL. Sequences similar to this domain were identified in Bax and Bip1, two other proteins that promote apoptosis and interact with Bcl-xL, and were likewise critical for their capacity to kill cells and bind Bcl-xL. Thus, the domain is of central importance in mediating the function of multiple cell death-regulatory proteins that interact with Bcl-2 family members.
Chittenden
T
T
Apoptosis Technology, Inc., Cambridge, MA 02139, USA.
Flemington
C
C
Houghton
A B
AB
Ebb
R G
RG
Gallo
G J
GJ
Elangovan
B
B
Chinnadurai
G
G
Lutz
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D017386:Sequence Homology, Amino Acid; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506: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; D051020:bcl-X Protein