Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2
The Bcl-2 (Bcl is B-cell lymphocytic-leukaemia proto-oncogene) family comprises two groups of proteins with distinct functional biology in cell-fate signalling. Bcl-2 protein was the first member to be discovered and associated with drug resistance in human lymphomas. Since then a host of other prot...
| Main Authors: | , , |
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| Format: | Journal Article |
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Portland Press Ltd.
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/51219 |
| _version_ | 1848758643485310976 |
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| author | Krishna, S. Low, I. Pervaiz, Shazib |
| author_facet | Krishna, S. Low, I. Pervaiz, Shazib |
| author_sort | Krishna, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The Bcl-2 (Bcl is B-cell lymphocytic-leukaemia proto-oncogene) family comprises two groups of proteins with distinct functional biology in cell-fate signalling. Bcl-2 protein was the first member to be discovered and associated with drug resistance in human lymphomas. Since then a host of other proteins such as Bcl-xL, Bcl-2A1 and Mcl-1 with similar anti-apoptotic functions have been identified. In contrast, the pro-apoptotic Bcl-2 proteins contain prototypic effector proteins such as Bax and Bak, and the BH3 (Bcl-2 homology)-only proteins comprising Bak, Bid, Bim, Puma and Noxa. A complex interplay between the association of pro-apoptotic and anti-apoptotic proteins with each other determines the sensitivity of cancer cells to drug-induced apoptosis. The canonical functional of Bcl-2 in terms of apoptosis inhibition is its ability to prevent mitochondrial permeabilization via inhibiting the translocation and oligomerization of proapoptotic proteins such as Bax; however, more recent evidence points to a novel mechanism of the anti-apoptotic activity of Bcl-2. Overexpression of Bcl-2 increases mitochondrial oxygen consumption and in doing so generates a slight pro-oxidant intracellular milieu, which promotes genomic instability and blocks death signalling. However, in the wake of overt oxidative stress, Bcl-2 regulates cellular redox status thereby preventing excessive build-up of ROS (reactive oxygen species), which is detrimental to cells and tissues. Taken together, the canonical and non-canonical activities of Bcl-2 imply a critical involvement of this protein in the processes of tumour initiation and progression. In the present paper we review these functionally distinct outcomes of Bcl-2 expression with implications for the chemotherapeutic management of cancers. © The Authors Journal compilation © 2011 Biochemical Society. |
| first_indexed | 2025-11-14T09:47:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-51219 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:47:15Z |
| publishDate | 2011 |
| publisher | Portland Press Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-512192017-09-13T15:34:50Z Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 Krishna, S. Low, I. Pervaiz, Shazib The Bcl-2 (Bcl is B-cell lymphocytic-leukaemia proto-oncogene) family comprises two groups of proteins with distinct functional biology in cell-fate signalling. Bcl-2 protein was the first member to be discovered and associated with drug resistance in human lymphomas. Since then a host of other proteins such as Bcl-xL, Bcl-2A1 and Mcl-1 with similar anti-apoptotic functions have been identified. In contrast, the pro-apoptotic Bcl-2 proteins contain prototypic effector proteins such as Bax and Bak, and the BH3 (Bcl-2 homology)-only proteins comprising Bak, Bid, Bim, Puma and Noxa. A complex interplay between the association of pro-apoptotic and anti-apoptotic proteins with each other determines the sensitivity of cancer cells to drug-induced apoptosis. The canonical functional of Bcl-2 in terms of apoptosis inhibition is its ability to prevent mitochondrial permeabilization via inhibiting the translocation and oligomerization of proapoptotic proteins such as Bax; however, more recent evidence points to a novel mechanism of the anti-apoptotic activity of Bcl-2. Overexpression of Bcl-2 increases mitochondrial oxygen consumption and in doing so generates a slight pro-oxidant intracellular milieu, which promotes genomic instability and blocks death signalling. However, in the wake of overt oxidative stress, Bcl-2 regulates cellular redox status thereby preventing excessive build-up of ROS (reactive oxygen species), which is detrimental to cells and tissues. Taken together, the canonical and non-canonical activities of Bcl-2 imply a critical involvement of this protein in the processes of tumour initiation and progression. In the present paper we review these functionally distinct outcomes of Bcl-2 expression with implications for the chemotherapeutic management of cancers. © The Authors Journal compilation © 2011 Biochemical Society. 2011 Journal Article http://hdl.handle.net/20.500.11937/51219 10.1042/BJ20101996 Portland Press Ltd. unknown |
| spellingShingle | Krishna, S. Low, I. Pervaiz, Shazib Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 |
| title | Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 |
| title_full | Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 |
| title_fullStr | Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 |
| title_full_unstemmed | Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 |
| title_short | Regulation of mitochondrial metabolism: Yet another facet in the biology of the oncoprotein Bcl-2 |
| title_sort | regulation of mitochondrial metabolism: yet another facet in the biology of the oncoprotein bcl-2 |
| url | http://hdl.handle.net/20.500.11937/51219 |