Expression of the adenovirus E1A gene in the rat thyroid differentiated cell line PC Cl 3 induces thyrotropin-independent cell growth and impairs differentiation. However, the malignant phenotype is achieved only when the PC E1A cells are infected with other murine retroviruses carrying the v-abl, v-raf or polyoma middle-T genes. To determine through which genes E1A affects thyroid cells, we differentially screened PC Cl 3 and PC E1A cells. Here we report a new gene, named CL2, that is upregulated in PC E1A cells. The CL2 transcript is 4.4 kb long and encodes a 949 amino-acid protein. Conceptual translation of the open reading frame showed one product with a signal peptide, multiple nuclear localization signals and three newly described domains. Furthermore, in vivo, this protein was located juxtanuclear, which is suggestive of Golgian localization, and also in cytoplasm and nucleus/nucleolus. Finally, CL2 gene expression was drastically downregulated in human thyroid neoplastic cell lines and tissues.