Cloning of the Human Interferon-Related Developmental Regulator (IFRD1) Gene Coding for the PC4 Protein, a Member of a Novel Family of Developmentally Regulated Genes

Abstract

The rat PC4 gene had been initially isolated as a nerve growth factor-inducible sequence in PC12 cells. Although its function remains unknown, recently it has been shown that PC4 is necessary to muscle differentiation and that it might have a role in signal transduction. We report the isolation of the human homolog of the rat PC4 gene, renamed here IFRD1 (interferon-related developmental regulator 1). Several human IFRD1 clones were identified by searching the EST database using the rat IFRD1 (PC4) cDNA as a query. An EST clone containing the entire ORF was chosen for sequencing. Human IFRD1 presented a predicted protein product of 453 amino acids, highly conserved (90.2% identity) compared to the rat IFRD1 (PC4) protein sequences. The mapping assignment of human IFRD1 to chromosome 7q22–q31 was retrieved from the UniGene database maintained at NCBI. A comparison of human IFRD1 (PC4) protein to databases revealed 47% identity to the protein encoded by the human gene SKMc15, originally isolated from a chromosome 3-specific library. Therefore, SKMc15 is a gene related to IFRD1, being the second member of a novel family. We analyzed their expression during murine development, and we found that mouse IFRD1 appears more expressed in specific differentiating structures at midgestation, while mouse SKMc15 is highly expressed soon after gastrulation and in the hepatic primordium, suggesting an involvement in early hematopoiesis.