Bax-mediated apoptosis modulating reagents and methods

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) C07K 14/47 (2006.01)

Patent

CA 2346070

The invention features substantially purified BAX polypeptides lacking either one of two specific domains, namely the ART domain or the transmembrane domain, within the BAX protein. Also disclosed are methods for identifying compounds which, when administered to a cell, increase or decrease apoptosis of the cell. These compounds are identified based on their abilities to interact with specific domains of the BAX protein, or to alter the interaction of the BAX ART domain with the BAX transmembrane domain. In addition, the invention provides methods for diagnosing a patient having, or predisposed to develop, a disease involving altered apoptosis by identifying a mutation in a BAX-encoding gene which results in an amino acid mutation in the BAX ART domain, a BAX transmembrane domain, or that alters the interaction of the BAX ART domain with the BAX transmembrane domain.

Cette invention a trait à des fragments polypeptidiques sensiblement purifiés appartenant à deux domaines spécifiques, en l'occurrence, le domaine ART et le domaine transmembranaire, de la protéine BAX qui, administrés à la cellule, accentuent ou modèrent l'apoptose cellulaire. On identifie ces composés en fonction de leur aptitude à interagir avec des domaines spécifiques de la protéine BAX, ou à modifier l'interaction du domaine ART de la protéine BAX avec le domaine transmembranaire de cette même protéine. L'invention porte, de surcroît, sur des méthodes permettant de diagnostiquer, chez un patient, un état pathologique modifiant l'apoptose ou bien une prédisposition à développer cet état et ce, par détection d'une mutation dans un gène codant la protéine BAX, laquelle mutation provoque une mutation d'acide aminé dans les domaines ART et transmembranaire de la protéine BAX ou modifie l'interaction du domaine ART avec le domaine transmembranaire de la protéine BAX.

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