Cross talk between cellular redox state and the antiapoptotic protein Bcl-2
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 cop...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Published: |
Mary Ann Liebert, Inc. Publishers
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/62093 |
| _version_ | 1848760786926698496 |
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| author | Pohl, Sebastian Agostino, Mark Dharmarajan, Arunasalam Pervaiz, Shazib |
| author_facet | Pohl, Sebastian Agostino, Mark Dharmarajan, Arunasalam Pervaiz, Shazib |
| author_sort | Pohl, Sebastian |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:21:19Z |
| format | Journal Article |
| id | curtin-20.500.11937-62093 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:21:19Z |
| publishDate | 2018 |
| publisher | Mary Ann Liebert, Inc. Publishers |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-620932019-02-19T05:36:18Z Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 Pohl, Sebastian Agostino, Mark Dharmarajan, Arunasalam Pervaiz, Shazib 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/62093 10.1089/ars.2017.7414 Mary Ann Liebert, Inc. Publishers fulltext |
| spellingShingle | Pohl, Sebastian Agostino, Mark Dharmarajan, Arunasalam Pervaiz, Shazib Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 |
| title | Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 |
| title_full | Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 |
| title_fullStr | Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 |
| title_full_unstemmed | Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 |
| title_short | Cross talk between cellular redox state and the antiapoptotic protein Bcl-2 |
| title_sort | cross talk between cellular redox state and the antiapoptotic protein bcl-2 |
| url | http://hdl.handle.net/20.500.11937/62093 |