Cited by 103Cell death mechanisms and regulationCancer-related Molecular PathwaysGenomics and Phylogenetic Studies

Evolution of Bcl-2 homology motifs: homology versus homoplasy

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Aouacheria, Abdel, Rech de Laval, Valentine, Combet, Christophe, Hardwick, J. Marie·2013·Trends in Cell Biology

Abstract

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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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)
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
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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