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BIK, the founding member of the BH3-only family proteins: mechanisms of cell death and role in cancer and pathogenic processes

Oncogene volume 27, pages S20–S29 (2008)Cite this article

Abstract

BIK is the founding member of the BH3-only family pro-apoptotic proteins. BIK is predominantly localized in the ER and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria and remodeling the mitochondrial cristae. BIK-mediated apoptosis is mediated by selective activation of BAX. BIK also induces non-apoptotic cell death in certain cell types by unknown mechanisms. BIK is non-essential for animal development, but appears to be functionally redundant for certain developmental functions with BIM. BIK is implicated in the selection of mature B cells in humans. BIK is a pro-apoptotic tumor suppressor in several human tissues and its expression in cancers is prevented by chromosomal deletions encompassing the Bik locus or by epigenetic silencing. BIK appears to be a critical effector in apoptosis induced by toxins, cytokines and virus infection. Several anti-cancer drugs transcriptionally activate Bik gene expression through transcriptional pathways dependent on factors such as E2F and p53 or by removal of epigenetic marks on the chromatin. BIK appears to be a prominent target for anti-cancer drugs that inhibit proteasomal functions. BIK has also been used as a therapeutic molecule in gene therapy-based approaches to treat difficult cancers.

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Acknowledgements

This study was supported by Grants CA-33616 and CA-73803 and from the National Cancer Institute. GC is grateful to Drs Thomas Chittenden and Robert Lutz (Immunogen Inc.) for valuable discussions that were critical in functional characterization of BIK. GC expresses his gratitude to Dr Walter Blättler (Immunogen Inc.) for his support and discussions. We thank Dr Marc Germain for his comments on this review.

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  1. Institute for Molecular Virology, Saint Louis University Health Sciences Center, Doisy Research Center, 1100 South Grand Blvd, St Louis, MO, USA

    G Chinnadurai & S Vijayalingam

  2. Department of Pediatrics, Saint Louis University Health Sciences Center, Doisy Research Center, 1100 South Grand Blvd, St Louis, MO, USA

    R Rashmi

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Correspondence to G Chinnadurai.

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Chinnadurai, G., Vijayalingam, S. & Rashmi, R. BIK, the founding member of the BH3-only family proteins: mechanisms of cell death and role in cancer and pathogenic processes. Oncogene 27 (Suppl 1), S20–S29 (2008). https://doi.org/10.1038/onc.2009.40

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