Abstract
BH3-only proteins function at a proximal point in a conserved cell death pathway by binding, through their BH3 domains, to other Bcl-2 family members and triggering mitochondrial events associated with apoptosis. Here, we describe a strongly pro-apoptotic BH3-only protein, designated Bbc3, whose expression increases in response to diverse apoptotic stimuli. bbc3 mRNA levels were induced by exposure to DNA-damaging agents and by wild-type p53, which mediates DNA damage-induced apoptosis. p53 transactivated bbc3 through consensus p53 binding sites within the bbc3 promoter region, indicating that bbc3 is a direct target of p53. Additionally, bbc3 mRNA was induced by p53-independent apoptotic stimuli, including dexamethasone treatment of thymocytes, and serum deprivation of tumor cells. Insulin-like growth factor-1 and epidermal growth factor, growth factors with broad anti-apoptotic activity, were each sufficient to suppress Bbc3 expression in serum-starved tumor cells. These results suggest that the transcriptional regulation of bbc3 contributes to the transduction of diverse cell death and survival signals.
Bibliography
Han, J., Flemington, C., Houghton, A. B., Gu, Z., Zambetti, G. P., Lutz, R. J., Zhu, L., & Chittenden, T. (2001). Expression of bbc3 , a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proceedings of the National Academy of Sciences, 98(20), 11318â11323.
References
37
Referenced
349
-
J M Adams, S Cory Science 281, 1322–1326 (1998).
(
10.1126/science.281.5381.1322) / Science by Adams J M (1998) - S J Korsmeyer Cancer Res 59, 1693s–1700s (1999). / Cancer Res by Korsmeyer S J (1999)
-
T Chittenden, E A Harrington, R O'Connor, C Flemington, R J Lutz, G I Evan, B C Guild Nature (London) 374, 733–736 (1995).
(
10.1038/374733a0) / Nature (London) by Chittenden T (1995) -
D C Huang, A Strasser Cell 103, 839–842 (2000).
(
10.1016/S0092-8674(00)00187-2) / Cell by Huang D C (2000) - H R Horvitz Cancer Res 59, 1701s–1706s (1999). / Cancer Res by Horvitz H R (1999)
-
J Zha, H Harada, E Yang, J Jockel, S J Korsmeyer Cell 87, 619–628 (1996).
(
10.1016/S0092-8674(00)81382-3) / Cell by Zha J (1996) -
X Luo, I Budihardjo, H Zou, C Slaughter, X Wang Cell 94, 481–490 (1998).
(
10.1016/S0092-8674(00)81589-5) / Cell by Luo X (1998) -
H Li, H Zhu, C J Xu, J Yuan Cell 94, 491–501 (1998).
(
10.1016/S0092-8674(00)81590-1) / Cell by Li H (1998) -
B Conradt, H R Horvitz Cell 93, 519–529 (1998).
(
10.1016/S0092-8674(00)81182-4) / Cell by Conradt B (1998) -
B Conradt, H R Horvitz Cell 98, 317–327 (1999).
(
10.1016/S0092-8674(00)81961-3) / Cell by Conradt B (1999) -
M M Metzstein, M O Hengartner, N Tsung, R E Ellis, H R Horvitz Nature (London) 382, 545–547 (1996).
(
10.1038/382545a0) / Nature (London) by Metzstein M M (1996) -
M M Metzstein, H R Horvitz Mol Cell 4, 309–319 (1999).
(
10.1016/S1097-2765(00)80333-0) / Mol Cell by Metzstein M M (1999) - C A Vater, L M Bartle, C A Dionne, T D Littlewood, V S Goldmacher Oncogene 13, 739–748 (1996). / Oncogene by Vater C A (1996)
-
E Yonish-Rouach, D Resnitzky, J Lotem, L Sachs, A Kimchi, M Oren Nature (London) 352, 345–347 (1991).
(
10.1038/352345a0) / Nature (London) by Yonish-Rouach E (1991) -
T Chittenden, C Flemington, A B Houghton, R G Ebb, G J Gallo, B Elangovan, G Chinnadurai, R J Lutz EMBO J 14, 5589–5596 (1995).
(
10.1002/j.1460-2075.1995.tb00246.x) / EMBO J by Chittenden T (1995) -
X M Zhou, Y Liu, G Payne, R J Lutz, T Chittenden J Biol Chem 275, 25046–25051 (2000).
(
10.1074/jbc.M002526200) / J Biol Chem by Zhou X M (2000) -
J Lin, J Chen, B Elenbaas, A J Levine Genes Dev 8, 1235–1246 (1994).
(
10.1101/gad.8.10.1235) / Genes Dev by Lin J (1994) -
A J Levine Cell 88, 323–331 (1997).
(
10.1016/S0092-8674(00)81871-1) / Cell by Levine A J (1997) -
K H Vousden Cell 103, 691–694 (2000).
(
10.1016/S0092-8674(00)00171-9) / Cell by Vousden K H (2000) -
W S el-Deiry, S E Kern, J A Pietenpol, K W Kinzler, B Vogelstein Nat Genet 1, 45–49 (1992).
(
10.1038/ng0492-45) / Nat Genet by el-Deiry W S (1992) -
S W Lowe, E M Schmitt, S W Smith, B A Osborne, T Jacks Nature (London) 362, 847–849 (1993).
(
10.1038/362847a0) / Nature (London) by Lowe S W (1993) -
A R Clarke, C A Purdie, D J Harrison, R G Morris, C C Bird, M L Hooper, A H Wyllie Nature (London) 362, 849–852 (1993).
(
10.1038/362849a0) / Nature (London) by Clarke A R (1993) -
Z Gu, C Flemington, T Chittenden, G P Zambetti Mol Cell Biol 20, 233–241 (2000).
(
10.1128/MCB.20.1.233-241.2000) / Mol Cell Biol by Gu Z (2000) -
T Miyashita, J C Reed Cell 80, 293–299 (1995).
(
10.1016/0092-8674(95)90513-8) / Cell by Miyashita T (1995) -
W S el-Deiry, T Tokino, V E Velculescu, D B Levy, R Parsons, J M Trent, D Lin, W E Mercer, K W Kinzler, B Vogelstein Cell 75, 817–825 (1993).
(
10.1016/0092-8674(93)90500-P) / Cell by el-Deiry W S (1993) -
H Dudek, S R Datta, T F Franke, M J Birnbaum, R Yao, G M Cooper, R A Segal, D R Kaplan, M E Greenberg Science 275, 661–665 (1997).
(
10.1126/science.275.5300.661) / Science by Dudek H (1997) -
R O'Connor, C Fennelly, D Krause Biochem Soc Trans 28, 47–51 (2000).
(
10.1042/bst0280047) / Biochem Soc Trans by O'Connor R (2000) -
K Nakano, K H Vousden Mol Cell 7, 683–694 (2001).
(
10.1016/S1097-2765(01)00214-3) / Mol Cell by Nakano K (2001) -
J Yu, L Zhang, P M Hwang, K W Kinzler, B Vogelstein Mol Cell 7, 673–682 (2001).
(
10.1016/S1097-2765(01)00213-1) / Mol Cell by Yu J (2001) -
E Oda, R Ohki, H Murasawa, J Nemoto, T Shibue, T Yamashita, T Tokino, T Taniguchi, N Tanaka Science 288, 1053–1058 (2000).
(
10.1126/science.288.5468.1053) / Science by Oda E (2000) -
C Sanz, A Benito, N Inohara, D Ekhterae, G Nunez, J L Fernandez-Luna Blood 95, 2742–2747 (2000).
(
10.1182/blood.V95.9.2742.009k24_2742_2747) / Blood by Sanz C (2000) -
T Shinjyo, R Kuribara, T Inukai, H Hosoi, T Kinoshita, A Miyajima, P J Houghton, A T Look, K Ozawa, T Inaba Mol Cell Biol 21, 854–864 (2001).
(
10.1128/MCB.21.3.854-864.2001) / Mol Cell Biol by Shinjyo T (2001) -
S R Datta, H Dudek, X Tao, S Masters, H Fu, Y Gotoh, M E Greenberg Cell 91, 231–241 (1997).
(
10.1016/S0092-8674(00)80405-5) / Cell by Datta S R (1997) -
S R Datta, A Brunet, M E Greenberg Genes Dev 13, 2905–2927 (1999).
(
10.1101/gad.13.22.2905) / Genes Dev by Datta S R (1999) -
P F Dijkers, R H Medemadagger, J W Lammers, L Koenderman, P J Coffer Curr Biol 10, 1201–1204 (2000).
(
10.1016/S0960-9822(00)00728-4) / Curr Biol by Dijkers P F (2000) -
T Inaba, T Inukai, T Yoshihara, H Seyschab, R A Ashmun, C E Canman, S J Laken, M B Kastan, A T Look Nature (London) 382, 541–544 (1996).
(
10.1038/382541a0) / Nature (London) by Inaba T (1996) -
T Inukai, A Inoue, H Kurosawa, K Goi, T Shinjyo, K Ozawa, M Mao, T Inaba, A T Look Mol Cell 4, 343–352 (1999).
(
10.1016/S1097-2765(00)80336-6) / Mol Cell by Inukai T (1999)
Dates
| Type | When |
|---|---|
| Created | 23 years ago (July 26, 2002, 10:37 a.m.) |
| Deposited | 3 years, 2 months ago (June 7, 2022, 1:26 a.m.) |
| Indexed | 5 days, 2 hours ago (Aug. 20, 2025, 8:27 a.m.) |
| Issued | 23 years, 11 months ago (Sept. 25, 2001) |
| Published | 23 years, 11 months ago (Sept. 25, 2001) |
| Published Online | 23 years, 11 months ago (Sept. 25, 2001) |
| Published Print | 23 years, 11 months ago (Sept. 25, 2001) |
@article{Han_2001, title={Expression of bbc3 , a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.201208798}, DOI={10.1073/pnas.201208798}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Han, Jia-wen and Flemington, Cathy and Houghton, Anne B. and Gu, Zhengming and Zambetti, Gerard P. and Lutz, Robert J. and Zhu, Li and Chittenden, Thomas}, year={2001}, month=sep, pages={11318–11323} }