CEFIP overexpression enhanced calcineurin-dependent hypertrophic signal transduction, while its knockdown repressed hypertrophy and calcineurin/NFAT activity in cardiomyocytes.
The novel z-disc protein CEFIP modulates calcineurin/NFAT signaling to regulate cardiomyocyte hypertrophy, offering a potential new mechanism in the pathogenesis of cardiomyopathy.
rotein (CEFIP), which exhibited a heart- and skeletal muscle-specific expression profile. Importantly, CEFIP was located at the z-disc and was up-regulated in several models of cardiomyopathy. We also found that CEFIP overexpression induced the fetal gene program and cardiomyocyte hypertrophy. Yeast two-hybrid screens revealed that CEFIP interacts with the calcineurin-binding protein four and a half LIM domains 2 (FHL2). Because FHL2 binds calcineurin, a phosphatase controlling hypertrophic signaling, we examined the effects of CEFIP on the calcineurin/nuclear factor of activated T-cell (NFAT) pathway. These experiments revealed that CEFIP overexpression further enhances calcineurin-dependent hypertrophic signal transduction, and its knockdown repressed hypertrophy and calcineurin/NFAT activity. In summary, we report on a previously uncharacterized protein CEFIP that modulates calcineurin/NFAT signaling in cardiomyocytes, a finding with possible implications for the pathogenesis of cardiomyopathy.
Dierck et al. (Tue,) conducted a other in Cardiomyopathy. CEFIP overexpression and knockdown was evaluated on Cardiomyocyte hypertrophy and calcineurin/NFAT signaling. CEFIP overexpression enhanced calcineurin-dependent hypertrophic signal transduction, while its knockdown repressed hypertrophy and calcineurin/NFAT activity in cardiomyocytes.