TSC-22 up-regulates collagen 3a1 gene expression in the rat heart.

Background: The transforming growth factor (TGF)-β is one of the key mediators in cardiac remodelling occurring after myocardial infarction (MI) and in hypertensive heart disease. The TGF-β-stimulated clone 22 (TSC-22) is a leucine zipper protein expressed in many tissues and possessing various transcription-modulating activities. However, its function in the heart remains unknown.

The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression.

The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects.

Characterization of the interaction between Actinin-Associated LIM Protein (ALP) and the rod domain of alpha-actinin.

Background: The PDZ-LIM proteins are a family of signalling adaptors that interact with the actin cross-linking protein, alpha-actinin, via their PDZ domains or via internal regions between the PDZ and LIM domains. Three of the PDZ-LIM proteins have a conserved 26-residue ZM motif in the internal region, but the structure of the internal region is unknown.

Results: In this study, using circular dichroism and nuclear magnetic resonance (NMR), we showed that the ALP internal region (residues 107-273) was largely unfolded in solution, but was able to interact with the alpha-actinin rod domain in vitro, and to co-localize with alpha-actinin on stress fibres in vivo.

The ZASP-like motif in actinin-associated LIM protein is required for interaction with the alpha-actinin rod and for targeting to the muscle Z-line.

The Z-line is a specialized structure connecting adjacent sarcomeres in muscle cells. alpha-Actinin cross-links actin filaments in the Z-line. Several PDZ-LIM domain proteins localize to the Z-line and interact with alpha-actinin.