The BH3-only protein bid is dispensable for DNA damage- and replicative stress-induced apoptosis or cell-cycle arrest.
Bid, a caspase-activated proapoptotic BH3-only protein, is essential for Fas-induced hepatocyte destruction. Recent studies published in Cell produced conflicting results, indicating that loss of Bid either protects or enhances apoptosis induced by DNA damage or replicative stress. To resolve this controversy, we generated novel Bid-deficient mice on an inbred C57BL/6 background and removed the drug-selection cassette from the targeted locus. Nine distinct cell types from these Bid-deficient mice underwent cell-cycle arrest and apoptosis in a manner indistinguishable from control WT cells in response to DNA damage or replicative stress. Moreover, we found that even cells from the original Bid-deficient mice responded normally to these stimuli, indicating that differences in genetic background or the presence of a strong promoter within the targeted locus are unlikely to explain the differences between our results and those reported previously. We conclude that Bid has no role in DNA damage- or replicative stress-induced apoptosis or cell-cycle arrest.
Kaufmann
Thomas
T
The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia.
Tai
Lin
L
Ekert
Paul G
PG
Huang
David C S
DC
Norris
Fiona
F
Lindemann
Ralph K
RK
Johnstone
Ricky W
RW
Dixit
Vishva M
VM
Strasser
Andreas
A
D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism*; D001773:Blood Cells / Q000166:cytology; D002453:Cell Cycle; D049109:Cell Proliferation; D003600:Cytosol / Q000737:chemistry; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; D008934:Mitogens