Transcriptional control of the calreticulin gene in health and disease.

Calreticulin is a multifunctional Ca(2+) binding chaperone in the endoplasmic reticulum and expression of the protein is tightly regulated at the transcriptional level. There are two calreticulin genes, named calreticulin-1 and calreticulin-2 gene. The calreticulin-1 promoter contains a number of putative binding sites for transcription factors including tissue specific factors. Direct regulation of the calreticulin-1 promoter by several of these factors has been confirmed experimentally including Nkx2.5, MEF2C, GATA6, PPAR, COUP-TF1 and Evi-1 factors. Studies on calreticulin-deficient mice and transgenic animal models indicate that calreticulin is critical for cardiac development and that expression of the protein must be tightly regulated during cardiogenesis. Moreover, differential expression of calreticulin has been associated with several diseases, including neurodegenerative problems, cancers, autoimmune diseases and wound healing. Understanding the mechanisms responsible for the regulation of expression of calreticulin may contribute to the treatment of many diverse diseases.