Molecular characterization of two novel PDZ-LIM proteins, Elfin (PDLIM1) and Mystique (PDLIM2).

摘要

The PDZ-LIM protein family is an emerging subclass of proteins which contains one PDZ motif at the amino terminus and one to three copies of LIM domains at the carboxyl terminus. Both PDZ and LIM domains are multifunctional protein-protein interaction motifs. Proteins with these motifs are usually involved in developmental regulation, cellular differentiation and cytoskeleton organization.; The PDZ-LIM family proteins have been suggested to act as adaptors that direct LIM/PDZ binding proteins to the cytoskeleton. Two novel PDZ-LIM proteins, Elfin (PDLIM1) and Mystique (PDLIM2), were identified during our laboratory's human EST sequencing projects. PDLIM1 is a 36kDa protein, which is abundantly expressed in heart and skeletal muscles. PDLIM1 was found to localize at the actin stress fibers by the green fluorescent protein (GFP) fusion technique. The specific localization of PDLIM1 suggested that it may have a regulatory role in cell morphology or cell movement. Previous findings showed that PDLIM1 interacted with α-actinin 2, an important structural component of sarcomere, through its LIM domain. In this study, PDLIM1 was shown to interact with calsarcin-1, a striated muscle-specific calcineurin-interacting protein that appears to function as a bridge between calcineurin and the contractile apparatus, via its PDZ domain. The interactions between PDLIM1 and calsarcin family members (calsarcin-1, calsarcin-2 and calsarcin-3) in vivo were confirmed by both the yeast and mammalian studies. Furthermore, we demonstrated that PDLIM1 gene expression was regulated under the control of calcineurin expression. We propose that PDLIM1 together with calsarcin-1 may form a protein complex which stabilizes the contractile apparatus in cardiac and skeletal muscles through the calcineurin mediated pathway.; Mystique (PDLIM2), a novel PDZ-LIM protein, is a 37 kDa protein identified from our human liver cancer cDNA sequencing project. The PDLIM2 transcript is widely distributed in a variety of human tissues. Its expression is relatively high in human liver, spleen, kidney and placenta. It was found to be overexpressed in the human hepatocarcinoma cell line, HepG2. Interestingly, this PDLIM2 gene was mapped by radiation hybrid assay to human chromosome 8p21.2, a region that is frequently deleted in common human cancers. (Abstract shortened by UMI.)