Methods and compositions relating to muscle selective...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) A61K 38/17 (2006.01) A61K 45/00 (2006.01) C07K 14/47 (2006.01) C12N 9/16 (2006.01) C12Q 1/68 (2006.01) G01N 33/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2415967

The present invention relates to the polypeptides known as muscle calcineurin interacting proteins (MCIPs). These molecules binding to calcineurin and, in so doing, modulate its functions, which includes phosphate removal as part of a pathway coupling Ca2+ to cellular responses in muscle. MCIPs form a physical complex with the catalytic subunit of calcineurin, and increased levels of MCIPs correspond to a reduced ability of calcineurin to stimulate transcription of certain target genes. Methods to exploit these observations are provided and include screening for modulators of MCIP expression and binding to calcineurin, methods of diagnosis of MCIP defects, and methods for treating cardiomyopathies, including cardiac hypertrophy.

Cette invention se rapporte à des polypeptides appelés protéines d'interaction de calcineurine musculaire (MCIP). Ces molécules se fixent à la calcineurine et, ce faisant, modulent ses fonctions, notamment l'élimination des phosphates comme partie d'une fonction canal de couplage de Ca?2+¿ aux réactions cellulaires dans le muscle. Les protéines MCIP forment un complexe physique avec la sous-unité catalytique de calcineurine et des niveaux accrus de MCIP correspondent à une aptitude réduite de la calcineurine à stimuler la transcription de certains gènes cibles. Cette invention décrit des procédés permettant de tirer profit de ces observations, tels que le criblage de modulateurs d'expression et de fixation de MCIP à la calcineurine, des procédés de diagnostic des défauts de MCIP et des procédés pour traiter les cardiomyopathies, y compris l'hypertrophie cardiaque.

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