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    Cross talk between cellular redox state and the antiapoptotic protein Bcl-2

    260110.pdf (1.529Mb)
    Access Status
    Open access
    Authors
    Pohl, Sebastian
    Agostino, Mark
    Dharmarajan, Arunasalam
    Pervaiz, Shazib
    Date
    2018
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Pohl, S. and Agostino, M. and Dharmarajan, A. and Pervaiz, S. 2018. Cross talk between cellular redox state and the antiapoptotic protein Bcl-2. Antioxidants & Redox Signaling. 29 (13): pp. 1215-1236.
    Source Title
    Antioxidants & Redox Signaling
    DOI
    10.1089/ars.2017.7414
    ISSN
    1557-7716
    School
    School of Pharmacy and Biomedical Sciences
    Remarks

    Final publication is available from Mary Ann Liebert, Inc., publishers at http://dx.doi.org/10.1089/ars.2017.7414

    URI
    http://hdl.handle.net/20.500.11937/62093
    Collection
    • Curtin Research Publications
    Abstract

    SIGNIFICANCE B cell lymphoma-2 (Bcl-2) is the prototypical anti-apoptotic member of the Bcl-2 family that comprises proteins with contrasting effects on cell fate. Identified as a consequence chromosomal translocation (t 14:18) in human lymphoma, subsequent studies have revealed mutations and/or copy number alterations, as well as post-translational modifications, of Bcl-2 in a variety of cancers. The canonical function of Bcl-2 is linked to its ability to inhibit mitochondrial membrane permeabilization, regulating apoptosome assembly and activation by blocking cytosolic translocation of death amplification factors. RECENT ADVANCES Aside from maintaining mitochondrial integrity, a novel facet of Bcl-2 biology involves crosstalk with cellular redox state. Bcl-2 overexpression modulates mitochondrial redox metabolism to create a 'pro-oxidant' milieu, conducive for cell survival. Under oxidative stress, Bcl-2 functions as a redox sink to prevent excessive build-up of reactive oxygen species, inhibiting execution signals. Evidence indicates various redox-dependent transcriptional changes and post-translational modifications with different functional outcomes. CRITICAL ISSUES Understanding the complex interplay between Bcl-2 and the cellular redox milieu from the standpoint of cell fate signaling remains vital for understanding pathological states associated with altered redox metabolism and/or aberrant Bcl-2 expression. FUTURE DIRECTIONS Small molecule inhibitors of Bcl-2 are showing promise in the clinic. The non-canonical activity linked to cellular redox metabolism provides a novel avenue for the design and development of diagnostic and therapeutic strategies against cancers refractory to conventional chemotherapy.

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