The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms
Intrinsic apoptosis, the response to intracellular cell death stimuli, is regulated by the interplay of the B-cell lymphoma 2 (Bcl-2) family and their membrane interactions. Bcl-2 proteins mediate a number of processes including development, homeostasis, autophagy, and innate and adaptive immune res...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/1/128 |
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| author | Suresh Banjara Chathura D. Suraweera Mark G. Hinds Marc Kvansakul |
| author_facet | Suresh Banjara Chathura D. Suraweera Mark G. Hinds Marc Kvansakul |
| author_sort | Suresh Banjara |
| collection | DOAJ |
| description | Intrinsic apoptosis, the response to intracellular cell death stimuli, is regulated by the interplay of the B-cell lymphoma 2 (Bcl-2) family and their membrane interactions. Bcl-2 proteins mediate a number of processes including development, homeostasis, autophagy, and innate and adaptive immune responses and their dysregulation underpins a host of diseases including cancer. The Bcl-2 family is characterized by the presence of conserved sequence motifs called Bcl-2 homology motifs, as well as a transmembrane region, which form the interaction sites and intracellular location mechanism, respectively. Bcl-2 proteins have been recognized in the earliest metazoans including Porifera (sponges), Placozoans, and Cnidarians (e.g., Hydra). A number of viruses have gained Bcl-2 homologs and subvert innate immunity and cellular apoptosis for their replication, but they frequently have very different sequences to their host Bcl-2 analogs. Though most mechanisms of apoptosis initiation converge on activation of caspases that destroy the cell from within, the numerous gene insertions, deletions, and duplications during evolution have led to a divergence in mechanisms of intrinsic apoptosis. Currently, the action of the Bcl-2 family is best understood in vertebrates and nematodes but new insights are emerging from evolutionarily earlier organisms. This review focuses on the mechanisms underpinning the activity of Bcl-2 proteins including their structures and interactions, and how they have changed over the course of evolution. |
| first_indexed | 2024-12-22T03:52:47Z |
| format | Article |
| id | doaj.art-10cbce7b28374d62bc852e762b7c2049 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-22T03:52:47Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-10cbce7b28374d62bc852e762b7c20492022-12-21T18:39:57ZengMDPI AGBiomolecules2218-273X2020-01-0110112810.3390/biom10010128biom10010128The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent MechanismsSuresh Banjara0Chathura D. Suraweera1Mark G. Hinds2Marc Kvansakul3Department of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, AustraliaDepartment of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, AustraliaBio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3052, AustraliaDepartment of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, AustraliaIntrinsic apoptosis, the response to intracellular cell death stimuli, is regulated by the interplay of the B-cell lymphoma 2 (Bcl-2) family and their membrane interactions. Bcl-2 proteins mediate a number of processes including development, homeostasis, autophagy, and innate and adaptive immune responses and their dysregulation underpins a host of diseases including cancer. The Bcl-2 family is characterized by the presence of conserved sequence motifs called Bcl-2 homology motifs, as well as a transmembrane region, which form the interaction sites and intracellular location mechanism, respectively. Bcl-2 proteins have been recognized in the earliest metazoans including Porifera (sponges), Placozoans, and Cnidarians (e.g., Hydra). A number of viruses have gained Bcl-2 homologs and subvert innate immunity and cellular apoptosis for their replication, but they frequently have very different sequences to their host Bcl-2 analogs. Though most mechanisms of apoptosis initiation converge on activation of caspases that destroy the cell from within, the numerous gene insertions, deletions, and duplications during evolution have led to a divergence in mechanisms of intrinsic apoptosis. Currently, the action of the Bcl-2 family is best understood in vertebrates and nematodes but new insights are emerging from evolutionarily earlier organisms. This review focuses on the mechanisms underpinning the activity of Bcl-2 proteins including their structures and interactions, and how they have changed over the course of evolution.https://www.mdpi.com/2218-273X/10/1/128apoptosisbcl-2evolutionmechanismstructure analysis |
| spellingShingle | Suresh Banjara Chathura D. Suraweera Mark G. Hinds Marc Kvansakul The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms Biomolecules apoptosis bcl-2 evolution mechanism structure analysis |
| title | The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms |
| title_full | The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms |
| title_fullStr | The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms |
| title_full_unstemmed | The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms |
| title_short | The Bcl-2 Family: Ancient Origins, Conserved Structures, and Divergent Mechanisms |
| title_sort | bcl 2 family ancient origins conserved structures and divergent mechanisms |
| topic | apoptosis bcl-2 evolution mechanism structure analysis |
| url | https://www.mdpi.com/2218-273X/10/1/128 |
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