TY - JOUR
T1 - Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-X(L) and promotes apoptosis
AU - Komatsu, Kiyoshi
AU - Miyashita, Toshiyuki
AU - Hang, Haiying
AU - Hopkins, Kevin M.
AU - Zheng, Wei
AU - Cuddeback, Sandy
AU - Yamada, Masao
AU - Lieberman, Howard B.
AU - Wang, Hong-Gang
N1 - Funding Information:
ACKNOWLEDGEMENTS We thank J. C. Reed and R. Jove for comments on the manuscript; S. Dalton for technical assistance; and the Molecular Biology, Flow Cytometry, and Molecular Imaging core facilities of Moffitt Cancer Center. This work was partially supported by grants from the ACS (IRG032) and NIH (CA82197-01) to H.-G.W., and grants from the NIH (GM52493 and CA68446) and DOE (DE-FG07-96ER62309) to H.B.L. Correspondence and requests for materials should be addressed to H.-G.W.
PY - 2000
Y1 - 2000
N2 - 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 antiapoptotic 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.
AB - 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 antiapoptotic 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.
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U2 - 10.1038/71316
DO - 10.1038/71316
M3 - Article
C2 - 10620799
AN - SCOPUS:0033794570
SN - 1465-7392
VL - 2
SP - 1
EP - 6
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 1
ER -