Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family
The B-cell lymphoma-2 (Bcl-2) family is a group of genes regulating intrinsic apoptosis, a process controlling events such as development, homeostasis and the innate and adaptive immune responses in metazoans. In higher organisms, Bcl-2 proteins coordinate intrinsic apoptosis through their regulatio...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Chathura D. Suraweera Suresh Banjara Mark G. Hinds Marc Kvansakul |
| author_facet | Chathura D. Suraweera Suresh Banjara Mark G. Hinds Marc Kvansakul |
| author_sort | Chathura D. Suraweera |
| collection | DOAJ |
| description | The B-cell lymphoma-2 (Bcl-2) family is a group of genes regulating intrinsic apoptosis, a process controlling events such as development, homeostasis and the innate and adaptive immune responses in metazoans. In higher organisms, Bcl-2 proteins coordinate intrinsic apoptosis through their regulation of the integrity of the mitochondrial outer membrane; this function appears to have originated in the basal metazoans. Bcl-2 genes predate the cnidarian-bilaterian split and have been identified in porifera, placozoans and cnidarians but not ctenophores and some nematodes. The Bcl-2 family is composed of two groups of proteins, one with an α-helical Bcl-2 fold that has been identified in porifera, placozoans, cnidarians, and almost all higher bilaterians. The second group of proteins, the BH3-only group, has little sequence conservation and less well-defined structures and is found in cnidarians and most bilaterians, but not porifera or placozoans. Here we examine the evolutionary relationships between Bcl-2 proteins. We show that the structures of the Bcl-2-fold proteins are highly conserved over evolutionary time. Some metazoans such as the urochordate <i>Oikopleura dioica</i> have lost all Bcl-2 family members. This gene loss indicates that Bcl-2 regulated apoptosis is not an absolute requirement in metazoans, a finding mirrored in recent gene deletion studies in mice. Sequence analysis suggests that at least some Bcl-2 proteins lack the ability to bind BH3-only antagonists and therefore potentially have other non-apoptotic functions. By examining the foundations of the Bcl-2 regulated apoptosis, functional relationships may be clarified that allow us to understand the role of specific Bcl-2 proteins in evolution and disease. |
| first_indexed | 2024-03-09T11:46:30Z |
| format | Article |
| id | doaj.art-68e8d760f09a4fca9111db4837d85633 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:46:30Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-68e8d760f09a4fca9111db4837d856332023-11-30T23:20:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237369110.3390/ijms23073691Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 FamilyChathura D. Suraweera0Suresh Banjara1Mark G. Hinds2Marc Kvansakul3Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, AustraliaBio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3052, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, AustraliaThe B-cell lymphoma-2 (Bcl-2) family is a group of genes regulating intrinsic apoptosis, a process controlling events such as development, homeostasis and the innate and adaptive immune responses in metazoans. In higher organisms, Bcl-2 proteins coordinate intrinsic apoptosis through their regulation of the integrity of the mitochondrial outer membrane; this function appears to have originated in the basal metazoans. Bcl-2 genes predate the cnidarian-bilaterian split and have been identified in porifera, placozoans and cnidarians but not ctenophores and some nematodes. The Bcl-2 family is composed of two groups of proteins, one with an α-helical Bcl-2 fold that has been identified in porifera, placozoans, cnidarians, and almost all higher bilaterians. The second group of proteins, the BH3-only group, has little sequence conservation and less well-defined structures and is found in cnidarians and most bilaterians, but not porifera or placozoans. Here we examine the evolutionary relationships between Bcl-2 proteins. We show that the structures of the Bcl-2-fold proteins are highly conserved over evolutionary time. Some metazoans such as the urochordate <i>Oikopleura dioica</i> have lost all Bcl-2 family members. This gene loss indicates that Bcl-2 regulated apoptosis is not an absolute requirement in metazoans, a finding mirrored in recent gene deletion studies in mice. Sequence analysis suggests that at least some Bcl-2 proteins lack the ability to bind BH3-only antagonists and therefore potentially have other non-apoptotic functions. By examining the foundations of the Bcl-2 regulated apoptosis, functional relationships may be clarified that allow us to understand the role of specific Bcl-2 proteins in evolution and disease.https://www.mdpi.com/1422-0067/23/7/3691apoptosisBcl-2evolutionsequence analysisstructure analysis |
| spellingShingle | Chathura D. Suraweera Suresh Banjara Mark G. Hinds Marc Kvansakul Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family International Journal of Molecular Sciences apoptosis Bcl-2 evolution sequence analysis structure analysis |
| title | Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family |
| title_full | Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family |
| title_fullStr | Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family |
| title_full_unstemmed | Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family |
| title_short | Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family |
| title_sort | metazoans and intrinsic apoptosis an evolutionary analysis of the bcl 2 family |
| topic | apoptosis Bcl-2 evolution sequence analysis structure analysis |
| url | https://www.mdpi.com/1422-0067/23/7/3691 |
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