Evolution of Bcl-2 homology motifs: homology versus homoplasy
Open accessAbstract
Bcl-2 family proteins regulate apoptosis in animals. This protein family includes several homologous proteins and a collection of other proteins lacking sequence similarity except for a Bcl-2 homology (BH)3 motif. Thus, membership in the Bcl-2 family requires only one of the four BH motifs. On this basis, a growing number of diverse BH3-only proteins are being reported. Although compelling cell biological and biophysical evidence validates many BH3-only proteins, claims of significant BH3 sequence similarity are often unfounded. Computational and phylogenetic analyses suggest that only some BH3 motifs arose by divergent evolution from a common ancestor (homology), whereas others arose by convergent evolution or random coincidence (homoplasy), challenging current assumptions about which proteins constitute the extended Bcl-2 family.
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In response to apoptotic stimuli, MOMP is mediated by BAX and/or BAK.
“In response to apoptotic stimuli, MOMP is mediated by BCL2 associated X, apoptosis regulator (BAX), and/or BCL2 antagonist/killer 1 (BAK1; best known as BAK), both of which contain four BH domains and a conserved transmembrane domain [44–46].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [46]
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- Authors
- Aouacheria, A., Rech de Laval, V., Combet, C., & Hardwick, J. M.
- Affiliations
- Lyon 1 Université (FR)
- Johns Hopkins University (US)
- Corresponding author
- Aouacheria, Abdel
- Hardwick, J. Marie
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 23
- Issue
- 3
- Pages
- 103-111
- ISSN
- 0962-8924 (ISSN-L)
- PMC
- PMC3582728
- OpenAlex
- W2025897016
- Cited by
- 103
- References
- 70
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 13 · 2017: 8 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 5
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM077875)
- National Institute of Neurological Disorders and Stroke (R01NS037402, R01 NS37402)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- Bcl-2 family proteins, BH3-only proteins, apoptosis regulation, homoplasy, convergent evolution, protein family evolution, phylogenetic analysis, sequence similarity
- MeSH terms
- Animals, Binding Sites, Humans, Molecular Sequence Data, Phylogeny, Apoptosis, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Evolution, Molecular, Proto-Oncogene Proteins c-bcl-2, Amino Acid Motifs
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