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Updated: Mar 26, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Sequence and partial functional analysis of canine Bcl-2 family proteins
S de Brot1, B Schade1, M Croci1
1Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, CH-8057 Zurich, Switzerland.
Abstract:
Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy. We have assessed the degree of conservation of a set of canine Bcl-2 family members with the human and murine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequences were analyzed, and their functional interactions were studied in yeasts. We found a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro-apoptotic Bax and Bak and anti-apoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systems based on canine-derived proteins might faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies with canine proteins.
Insights
Canine Bcl-2 family proteins show high sequence similarity to human counterparts, suggesting dogs as a model for cancer research. Yeast functional studies confirm conserved interactions, validating canine proteins for comparative oncology studies.
Area of Science:
- Comparative oncology and molecular biology.
- Investigating the conservation of apoptosis-regulating proteins between species.
Background:
- Spontaneous canine neoplasms share biological similarities with human cancers.
- Apoptotic pathways are crucial in cancer development and therapeutic responses.
- The Bcl-2 family of proteins plays a key role in regulating apoptosis.
Purpose of the Study:
- To assess the conservation of canine Bcl-2 family members compared to human and murine orthologs.
- To analyze the functional interactions of these canine proteins.
Main Methods:
- Cloning of seven complete canine Bcl-2 family open reading frames, including four novel sequences.
- Sequence analysis of cloned canine proteins.
- Functional interaction studies using yeast as a model system.
Main Results:
- High overall and domain sequence homology was observed between canine and human Bcl-2 family proteins, exceeding that between murine and human proteins.
- Functional interactions between canine pro-apoptotic proteins (Bax, Bak) and anti-apoptotic proteins (Bcl-xL, Bcl-w, Mcl-1) were successfully recapitulated in yeast.
- Four novel canine Bcl-2 family member sequences were identified and characterized.
Conclusions:
- Canine Bcl-2 family proteins exhibit significant homology to their human counterparts.
- Yeast systems can faithfully reproduce Bcl-2 family member interactions, establishing yeast as a valuable tool for functional studies of canine proteins.
- These findings support the utility of canine models for studying cancer biology and therapeutic strategies relevant to human diseases.
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