Identification of two novel mRNA splice variants of bax

Al, Thomas; Price, Christopher E.; Martin, Stewart G.; Carmichael, J.; Jc, Murray

doi:10.1038/sj.cdd.4400474

Cited by 12 publications

(5 citation statements)

References 3 publications

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“…An exception in this group is Bcl-X S , which in addition to the C-terminal domain has only the BH3 and BH4 domains. Several spliced variants of Bax have been identified (Apte et al 1995;Zhou et al 1998; Thomas et al 1999), one splice variant of Bok has also been described (Hsu and Hsueh 1998), and recently a neuron-specific splicing variant of Bak was described (Sun et al 2001). However, the function of these various forms of the proteins still remains unknown.…”

Section: The Proteinsmentioning

confidence: 96%

Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion

Antonsson¹

2001

Cell Tissue Res

296

202

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Two major intracellular apoptosis signaling cascades have been characterized, the mitochondrial pathway and the death receptor pathway. The mitochondrial pathway is regulated by members of the Bcl-2 protein family. The members of this family can be subdivided into anti- and pro-apoptotic proteins. The pro-apoptotic members are further divided into two groups, the multidomain and the 'BH3 domain only' proteins. When cells are exposed to apoptotic stimulation, pro-apoptotic proteins are activated through post-translational modifications or changes in their conformation. The main site of action of the multidomain proteins are the mitochondria, where these proteins induce permeabilization of the outer membrane resulting in the release of proteins, including cytochrome c, from the intermembrane space. In the cytosol cytochrome c activates caspase cascades ultimately leading to cell death. Mounting evidence indicates that apoptosis is involved in a wide range of pathological conditions. Recent studies suggest that the mitochondrial signaling pathway is involved in several diseases. Although, so far, with the exception of C. elegans, most studies on apoptosis have been performed in mammalian systems, recently homologues to the Bcl-2 family members, including pro-apoptotic members, have been identified in Drosophila and zebrafish. Here the structure and function of the various pro-apoptotic Bcl-2 family members, their effects on mitochondria, and their involvement in diseases are discussed.

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Section: The Proteinsmentioning

confidence: 96%

Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion

Antonsson¹

2001

Cell Tissue Res

296

202

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“…Upon stimulation by a death signal, Bax translocates to the mitochondrial membrane where it disrupts the mitochondrial membrane, causes the release of cytochrome C, and sequentially activates caspase-9 and caspase-3 for cell death (24,25). Bax has several isoforms, mostly generated by alternative splicing between exon 1 and exon 3 or between exon 5 and exon 6 from the prototype Baxa pre-mRNA (21,(26)(27)(28)(29)(30). These isoforms either universally exist in normal and cancer cells or are only detectable in certain tissues (29).…”

Section: Introductionmentioning

confidence: 99%

BaxΔ2 Promotes Apoptosis through Caspase-8 Activation in Microsatellite-Unstable Colon Cancer

Zhang¹,

Lin²,

Mañas³

et al. 2014

Molecular Cancer Research

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Loss of apoptotic Bax due to microsatellite mutation contributes to tumor development and chemoresistance. Recently, a Bax microsatellite mutation was uncovered in combination with a specific alternative splicing event that could generate a unique Bax isoform (BaxD2) in otherwise Bax-negative cells. Like the prototype Baxa, BaxD2 is a potent proapoptotic molecule. However, the proapoptotic mechanism and therapeutic implication of BaxD2 remain elusive. Here, the isolation and analysis of isogenic subcell lines are described that represent different Bax microsatellite statuses from colorectal cancer. Colon cancer cells harboring Bax microsatellite G7/G7 alleles are capable of producing low levels of endogenous BaxD2 transcripts and proteins. Interestingly, BaxD2-positive cells are selectively sensitive to a subgroup of chemotherapeutics compared with BaxD2-negative cells. Unlike other Bax isoforms, BaxD2 recruits caspase-8 into the proximity for activation, and the latter, in turn, activates caspase-3 and apoptosis independent of the mitochondrial pathway. These data suggest that the expression of BaxD2 may provide alternative apoptotic and chemotherapeutic advantages for Bax-negative tumors.

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“…The Bax subfamily includes the prototypical Bax␣ and several alternatively spliced isoforms such as Bax␤, , , ␥, , and ␦ (13)(14)(15)(16)(17)(18)(19). Bax␣ consists of six exons encoding a number of functional domains that regulate Bax subcellular localization and pro-death activity (16,20).…”

mentioning

confidence: 99%

BaxΔ2 Is a Novel Bax Isoform Unique to Microsatellite Unstable Tumors

Haferkamp

Zhang

Lin

et al. 2012

Journal of Biological Chemistry

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Background: Mutations and alternative splicing often silence tumor suppressor gene expression, promoting tumor development. Results: A novel Bax isoform (Bax⌬2) generated from the combination of a microsatellite deletion and unexpected splicing promotes unconventional cell death. Conclusion: Bax⌬2 is an MSI tumor-specific pro-death Bax isoform. Significance: Alternative splicing of mutated gene can restore tumor suppressor function and can be detrimental to the tumors.

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Identification of two novel mRNA splice variants of bax

Cited by 12 publications

References 3 publications

Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion

Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion

BaxΔ2 Promotes Apoptosis through Caspase-8 Activation in Microsatellite-Unstable Colon Cancer

BaxΔ2 Is a Novel Bax Isoform Unique to Microsatellite Unstable Tumors

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