Inhibition of transcriptional activities of AP-1 and c-Jun by a new zinc finger protein ZNF394

Zinc finger proteins play important roles in a variety of cellular functions, including cell growth, proliferation, apoptosis, and intracellular signal transduction, and the zinc finger-containing transcription factor has been implicated as a critical regulator of multiple cardiac-expressed genes as well as a regulator of inducible gene expression in response to hypertrophic stimulation. With the aim of identifying the genes involved in human heart development and diseases, we have isolated a novel LER-related zinc finger gene named ZNF394 from human heart cDNA library. ZNF394 gene has a predicted 561-amino acid open reading frame, encoding a 64kDa zinc finger protein. The N-terminus of ZNF394 protein has a leucine-rich region (LER or SCAN domain), followed by a well-conserved kruppel-associated box domain. The C-terminus of the protein contains 7 C₂H₂ zinc finger motifs in tandem arrays with the highly conserved space region of the H/C-link. ZNF394 gene is mapped to chromosome 7q11.21. Northern blot analysis indicates that a 2.18kb transcript specific for ZNF394 is specifically expressed in the heart, skeletal muscle, and brain in human adult tissues. ZNF394 protein is expressed in cell nucleus. Overexpression of ZNF394 in the cell inhibits the transcriptional activities of c-Jun and AP-1 reporters, suggesting that ZNF394 is a new transcriptional repressor in mitogen-activated protein kinase signaling pathways and may play an important role in cardiac development and/or cardiac function.