Expression of Bbc3, a Pro-apoptotic BH3-only Gene, is Regulated by Diverse Cell Death and Survival Signals

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2001 Sep 27

PMID 11572983

Citations 186

Authors

J Han

C Flemington

A B Houghton

Z Gu

G P Zambetti

R J Lutz

L Zhu

T Chittenden

Affiliations

Soon will be listed here.

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.

Citing Articles

Chronic social instability stress differentially affects the behavior and the transcriptome of the anterodorsal bed nucleus of the stria terminalis between male and female mice.

Degroat T, Paladino S, Denney K, Moran K, Samuels B, Roepke T bioRxiv. 2025; .

PMID: 39896497 PMC: 11785045. DOI: 10.1101/2025.01.21.634142.

Identification of the whole genome of alternative splicing and RNA-binding proteins involved in nintedanib-induced apoptosis in gastric cancer cells.

Dong X, Liu Z, Yu M, Yang X, Cai H PeerJ. 2024; 12:e18697.

PMID: 39726754 PMC: 11670762. DOI: 10.7717/peerj.18697.

Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development.

Matsumoto K, Akieda Y, Haraoka Y, Hirono N, Sasaki H, Ishitani T Nat Commun. 2024; 15(1):10662.

PMID: 39690179 PMC: 11652645. DOI: 10.1038/s41467-024-55108-x.

Genome-Wide Analysis of p53 Targets Reveals SCN2A as a Novel Player in p53-Induced Cell Arrest in HPV-Positive Cells.

Zhang Y, Liu Y, Xing X, Liu H, Guan W Viruses. 2024; 16(11).

PMID: 39599840 PMC: 11598893. DOI: 10.3390/v16111725.

Human Multi-Lineage Liver Organoid Model Reveals Impairment of CYP3A4 Expression upon Repeated Exposure to Graphene Oxide.

Romaldini A, Spano R, Veronesi M, Grimaldi B, Bandiera T, Sabella S Cells. 2024; 13(18.

PMID: 39329726 PMC: 11429598. DOI: 10.3390/cells13181542.

References

Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun R, Canman C . Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. Nature. 1996; 382(6591):541-4. DOI: 10.1038/382541a0. View

Chittenden T, Flemington C, Houghton A, Ebb R, Gallo G, Elangovan B . A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995; 14(22):5589-96. PMC: 394673. DOI: 10.1002/j.1460-2075.1995.tb00246.x. View

Vater C, Bartle L, Dionne C, Littlewood T, Goldmacher V . Induction of apoptosis by tamoxifen-activation of a p53-estrogen receptor fusion protein expressed in E1A and T24 H-ras transformed p53-/- mouse embryo fibroblasts. Oncogene. 1996; 13(4):739-48. View

Zha J, Harada H, Yang E, Jockel J, Korsmeyer S . Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 1996; 87(4):619-28. DOI: 10.1016/s0092-8674(00)81382-3. View

Dudek H, Datta S, Franke T, Birnbaum M, Yao R, Cooper G . Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 1997; 275(5300):661-5. DOI: 10.1126/science.275.5300.661. View

Levine A . p53, the cellular gatekeeper for growth and division. Cell. 1997; 88(3):323-31. DOI: 10.1016/s0092-8674(00)81871-1. View

Datta S, Dudek H, Tao X, Masters S, Fu H, Gotoh Y . Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997; 91(2):231-41. DOI: 10.1016/s0092-8674(00)80405-5. View

Conradt B, Horvitz H . The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell. 1998; 93(4):519-29. DOI: 10.1016/s0092-8674(00)81182-4. View

Luo X, Budihardjo I, Zou H, Slaughter C, Wang X . Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998; 94(4):481-90. DOI: 10.1016/s0092-8674(00)81589-5. View

10.

Li H, Zhu H, Xu C, Yuan J . Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998; 94(4):491-501. DOI: 10.1016/s0092-8674(00)81590-1. View

11.

Adams J, Cory S . The Bcl-2 protein family: arbiters of cell survival. Science. 1998; 281(5381):1322-6. DOI: 10.1126/science.281.5381.1322. View

12.

Korsmeyer S . BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 1999; 59(7 Suppl):1693s-1700s. View

13.

Horvitz H . Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res. 1999; 59(7 Suppl):1701s-1706s. View

14.

Conradt B, Horvitz H . The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene. Cell. 1999; 98(3):317-27. DOI: 10.1016/s0092-8674(00)81961-3. View

15.

Metzstein M, Horvitz H . The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein. Mol Cell. 1999; 4(3):309-19. DOI: 10.1016/s1097-2765(00)80333-0. View

16.

Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K . SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Mol Cell. 1999; 4(3):343-52. DOI: 10.1016/s1097-2765(00)80336-6. View

17.

Datta S, Brunet A, Greenberg M . Cellular survival: a play in three Akts. Genes Dev. 1999; 13(22):2905-27. DOI: 10.1101/gad.13.22.2905. View

18.

Gu Z, Flemington C, Chittenden T, Zambetti G . ei24, a p53 response gene involved in growth suppression and apoptosis. Mol Cell Biol. 1999; 20(1):233-41. PMC: 85079. DOI: 10.1128/MCB.20.1.233-241.2000. View

19.

Sanz C, Benito A, Inohara N, Ekhterae D, Nunez G, Fernandez-Luna J . Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells. Blood. 2000; 95(9):2742-7. View

20.

Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T . Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 2000; 288(5468):1053-8. DOI: 10.1126/science.288.5468.1053. View