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Bfl-1S, a novel alternative splice variant of Bfl-1, localizes in the nucleus via its C-terminus and prevents cell death

Oncogene volume 22, pages 2457–2465 (2003)Cite this article

Abstract

Bfl-1 is an antiapoptotic Bcl-2 family member and a mouse A1 homologue. The mouse A1 has been reported to have three isoforms, but little is known about human Bfl-1. By reverse–transcriptase polymerase chain reaction analysis, we have identified Bfl-1S (short form), an alternative splice variant of Bfl-1. The Bfl-1S primary sequence contains four conserved Bcl-2 homology (BH) domains and a positive-charged C-terminus containing KKRK amino acids. The expression of Bfl-1S mRNA was detected predominantly in normal lymph nodes and in B-lymphoid leukemia cells. Confocal microscopic analysis using green fluorescence protein fusion proteins demonstrated that Bfl-1S is localized in the nucleus by its C-terminus as an intrinsic nuclear localization sequence. Bfl-1S acts as an antiapoptotic agent in coexpression experiments with Bax, a proapoptotic molecule. The expression of Bfl-1S provided significant resistance against staurosporine (STS) treatments in Molt-4 human T-leukemia cells. Bfl-1S also significantly inhibited the cleavage of Bid, and of caspases 3 and 8 against STS treatment. These results indicate that Bfl-1S is a novel human Bcl-2 family member that possesses antiapoptotic function.

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Abbreviations

RT–PCR:

reverse–transcriptase polymerase chain reaction

PI:

propidium iodide

GFP:

green fluorescence protein

BH domain:

Bcl-2 homology domain

NLS:

nuclear localization sequence

STS:

staurosporine

CHX:

cycloheximide

5-FU:

5-fluorouracil

ΔΨm:

mitochondrial transmembrane potential

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Acknowledgements

This work was supported by grants from the Korea Ministry of Health and Welfare (01-PJ1-PG3-20700-0033) and Seoul National University Hospital (03-2002-051). We thank Dr Masao Seto for a critical reading of this manuscript and helpful discussions.

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Author notes

  1. Jae-Kyun Ko and Min-Jung Lee: The authors contributed equally to this paper.

Authors and Affiliations

  1. Department of Pathology, Tumor Immunity Medical Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Jae-Kyun Ko, Min-Jung Lee, Jung-Ah Cho, Bo-Young Lee & Chul-Woo Kim

  2. The Institute of iNtRON Biotechnology, Seoul, Korea

    Sun-Hee Cho

  3. Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA

    Jason Soonju Koh

  4. Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul, Korea

    Seung-Sook Lee

  5. Department of Biological Sciences, Konkuk University, Seoul, Korea

    Yhong-Hee Shim

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  1. Jae-Kyun Ko
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Correspondence to Chul-Woo Kim.

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Ko, JK., Lee, MJ., Cho, SH. et al. Bfl-1S, a novel alternative splice variant of Bfl-1, localizes in the nucleus via its C-terminus and prevents cell death. Oncogene 22, 2457–2465 (2003). https://doi.org/10.1038/sj.onc.1206274

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