Calretinin (CR) is an EF-hand calcium binding protein expressed in a tissue-specific manner. CR gene is active in some neurons, such as cerebellar granule neurons and in some tumor cells such as colon adenocarcinoma or epithelial mesothelioma. Our aim was to understand the mechanism(s) involved in tissue-specific regulation of CR gene transcription. Our recent paper showed that an "AP2-like" sequence located between -90/-80 bp of the CR gene promoter is important for specific expression of this gene in neurons differentiating from DEV multipotent cells [Biochim. Biophys. Acta (1577) 2000 412]. We now show by electrophoretic mobility shift assay (EMSA) that in cerebellar granule neurons, there is a nuclear protein that interacts with the "AP2-like" sequence. This interaction results in an increased CR gene promoter activity. In contrast, the "AP2-like" sequence does not play such a role in regulation of the CR gene transcription in adenocarcinoma and mesothelioma cancer cells. In these cells mutation in the "AP2-like" element did not affect transcriptional activity of the CR gene promoter and no protein binding to this element was observed by EMSA. These data clearly show that expression of CR gene in neurons and cancer cells is regulated by different mechanisms. On the other hand, in both cell types, the activity of CR gene promoter can be stimulated by zinc ions.