Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis.
DNA damage induces apoptosis through a signalling pathway that can be suppressed by the BCL-2 protein, but the mechanism by which DNA damage does this is unknown. Here, using yeast two-hybrid and co-immunoprecipitation studies, we show that RAD9, a human protein involved in the control of a cell-cycle checkpoint, interacts with the anti-apoptotic Bcl-2-family proteins BCL-2 and BCL-x L, but not with the pro-apoptotic BAX and BAD. When overexpressed in mammalian cells, RAD9 induces apoptosis that can be blocked by BCL-2 or BCL-x L. Conversely, antisense RAD9 RNA suppresses cell death induced by methyl methanesulphonate. These findings indicate that RAD9 may have a new role in regulating apoptosis after DNA damage, in addition to its previously described checkpoint-control and other radioresistance-promoting functions.
Komatsu
K
K
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
Miyashita
T
T
Hang
H
H
Hopkins
K M
KM
Zheng
W
W
Cuddeback
S
S
Yamada
M
M
Lieberman
H B
HB
Wang
H G
HG
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry; D002470:Cell Survival / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007202:Indicators and Reagents; D008322:Mammals; D008969:Molecular Sequence Data; D010957:Plasmids; D011419:Propidium; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000494:pharmacology; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D018797:Cell Cycle Proteins; D007202:Indicators and Reagents; D019253:Proto-Oncogene Proteins c-bcl-2; D016372:RNA, Antisense; D051020:bcl-X Protein; C069930:rad9 protein; D011419:Propidium