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Publication : BaxΔ2 is a novel bax isoform unique to microsatellite unstable tumors.

First Author  Haferkamp B Year  2012
Journal  J Biol Chem Volume  287
Issue  41 Pages  34722-9
PubMed ID  22910913 Mgi Jnum  J:192965
Mgi Id  MGI:5467167 Doi  10.1074/jbc.M112.374785
Citation  Haferkamp B, et al. (2012) BaxDelta2 is a novel bax isoform unique to microsatellite unstable tumors. J Biol Chem 287(41):34722-9
abstractText  The pro-death Bcl-2 family protein and tumor suppressor Bax is frequently mutated in tumors with microsatellite instability (MSI). The mutation often results in a "Bax negative" phenotype and therefore is generally thought to be beneficial to the development of the tumor. Here, we report the identification of a novel Bax isoform, BaxDelta2, which is unique to microsatellite unstable tumors. BaxDelta2 is generated by a unique combination of a microsatellite deletion in Bax exon 3 and alternative splicing of Bax exon 2. Consistently, BaxDelta2 is only detected in MSI cell lines and primary tumors. BaxDelta2 is a potent cell death inducer but does not directly target mitochondria. In addition, BaxDelta2 sensitizes certain MSI tumor cells to a subset of chemotherapeutic agents, such as adriamycin. Thus, our data provide evidence that mutation and alternative splicing of tumor suppressors such as Bax are not always beneficial to tumor development but can be detrimental instead.
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