Abstract
Proteins of the Bcl-2 family are critical regulators of apoptosis. Proapoptotic members, like Bax, contain three of the four Bcl-2 homology regions (BH1-3), while BH3-only proteins, like Bim, possess only the short BH3 motif. Database searches revealed Bfk, an unusual novel member of the Bcl-2 family that contains a BH2 and BH3 region but not BH1 or BH4. Bfk is thus most closely related to Bcl-GL. It lacks a C-terminal membrane anchor and is cytosolic. Enforced expression of Bfk weakly promoted apoptosis and antagonized Bcl-2's prosurvival function. Like Bcl-GL, Bfk did not bind to any Bcl-2 family members, even though its BH3 motif can mediate association with prosurvival proteins. Low amounts of Bfk were found in stomach, ovary, bone marrow and spleen, but its level in the mammary gland rose markedly during pregnancy, suggesting that Bfk may play a role in mammary development.
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Abbreviations
- BH:
-
Bcl-2 homology
- Bfk:
-
Bcl-2 family kin
- EST:
-
expressed sequence tag
- ORF:
-
open reading frame
- HA:
-
hemagglutinin
- MiT:
-
MSCV-IRES-Thy1.1
- MSCV:
-
mouse stem cell virus
- IRES:
-
internal ribosome entry site
- PI:
-
propidium iodide
- PCR:
-
polymerase chain reaction
- SDS:
-
sodium dodecyl sulfate
- DME:
-
Dulbecco's modified Eagle
- FCS:
-
fetal calf serum
- PAGE:
-
polyacrylamide gel electrophoresis
- FITC:
-
fluorescein isothiocyanate
- DAPI:
-
4′6-diamidino-2-phenylindole dihydrochloride
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Acknowledgements
We thank Drs. D Hildeman and P Marrack for the MiT retroviral vector, C Chang and B Duscio for technical assistance, Dr. H Puthalakath for help with yeast two-hybrid analysis, Dr. L O'Reilly and J Jimenez for help with protein and antibody production and Dr. F Battye, C Tarlinton, J Chan, D Kaminaris, V Lapatis and Dr. L O'Reilly for help with flow cytometry and confocal microscopy. We are grateful to Drs. A Harris, H Puthalakath and P Bouillet for insightful discussions and critical comments on the manuscript. This work was supported by fellowships and grants from the NHMRC (Canberra), the Dr. Josef Steiner Cancer Research Foundation (Bern), the Sylvia and Charles Viertel Charitable Foundation, the Leukemia and Lymphoma Society of America and the NIH (CA80188).
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Coultas, L., Pellegrini, M., Visvader, J. et al. Bfk: a novel weakly proapoptotic member of the Bcl-2 protein family with a BH3 and a BH2 region. Cell Death Differ 10, 185–192 (2003). https://doi.org/10.1038/sj.cdd.4401204
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DOI: https://doi.org/10.1038/sj.cdd.4401204
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