Sequence and partial functional analysis of canine Bcl-2 family proteins

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 ortholo...

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Bibliographic Details
Published in:Research in veterinary science 2016-02, Vol.104, p.126-135
Main Authors: de Brot, S., Schade, B., Croci, M., Dettwiler, M., Guscetti, F.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bcl-2 family
Cancer
Canine
Cloning
Cloning, Molecular
Comparative sequence analysis
Cytochrome
DNA, Complementary - genetics
DNA, Complementary - metabolism
Dogs
Dogs - genetics
Dogs - metabolism
Functional yeast study
Genomes
Laboratories
Molecular Sequence Data
Open Reading Frames
Organisms, Genetically Modified - metabolism
Proteins
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Saccharomyces cerevisiae - metabolism
Sequence Analysis, DNA
Tumorigenesis
Tumors
Veterinary medicine
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Summary: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. •We have cloned selected canine Bcl-2 family members and analyzed their sequences.•Canine Bcl-2 proteins display a high degree of homology with their human counterparts.•We have successfully established a yeast model for functional studies of canine Bcl-2 proteins.
ISSN:0034-5288
1532-2661
DOI:10.1016/j.rvsc.2015.12.001