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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Main Authors: de Brot, Simone, Schade, Benjamin, Croci, Martina, Dettwiler, Martina, Guscetti, Franco
Format: Article
Published: Elsevier 2016
Subjects:
Online Access:https://eprints.nottingham.ac.uk/37341/
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author de Brot, Simone
Schade, Benjamin
Croci, Martina
Dettwiler, Martina
Guscetti, Franco
author_facet de Brot, Simone
Schade, Benjamin
Croci, Martina
Dettwiler, Martina
Guscetti, Franco
author_sort de Brot, Simone
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-373412020-05-04T17:35:09Z https://eprints.nottingham.ac.uk/37341/ Sequence and partial functional analysis of canine Bcl-2 family proteins de Brot, Simone Schade, Benjamin Croci, Martina Dettwiler, Martina Guscetti, Franco 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. Elsevier 2016-02-28 Article PeerReviewed de Brot, Simone, Schade, Benjamin, Croci, Martina, Dettwiler, Martina and Guscetti, Franco (2016) Sequence and partial functional analysis of canine Bcl-2 family proteins. Research in Veterinary Science, 104 . pp. 126-135. ISSN 1532-2661 Bcl-2 family; Canine; Cloning; Comparative sequence analysis; Functional yeast study http://www.sciencedirect.com/science/article/pii/S0034528815301028 doi:10.1016/j.rvsc.2015.12.001 doi:10.1016/j.rvsc.2015.12.001
spellingShingle Bcl-2 family; Canine; Cloning; Comparative sequence analysis; Functional yeast study
de Brot, Simone
Schade, Benjamin
Croci, Martina
Dettwiler, Martina
Guscetti, Franco
Sequence and partial functional analysis of canine Bcl-2 family proteins
title Sequence and partial functional analysis of canine Bcl-2 family proteins
title_full Sequence and partial functional analysis of canine Bcl-2 family proteins
title_fullStr Sequence and partial functional analysis of canine Bcl-2 family proteins
title_full_unstemmed Sequence and partial functional analysis of canine Bcl-2 family proteins
title_short Sequence and partial functional analysis of canine Bcl-2 family proteins
title_sort sequence and partial functional analysis of canine bcl-2 family proteins
topic Bcl-2 family; Canine; Cloning; Comparative sequence analysis; Functional yeast study
url https://eprints.nottingham.ac.uk/37341/
https://eprints.nottingham.ac.uk/37341/
https://eprints.nottingham.ac.uk/37341/