An efficient expression cloning system for the isolation of new transforming genes was developed. cDNA expression libraries from a melanoma (A101D) and from a lung epithelial tumor cell line (A549) were constructed and transfected into NIH/3T3 cells. Morphologically transformed cells were isolated, expanded and plasmids containing transforming sequences were rescued. Several previously known oncogenes were present in both libraries. Additionally, a new transforming sequence was isolated from the A101D melanoma library. This new sequence has an opening reading frame of 1120 nucleotides, and the translated produce is homologous to a gene product expressed in proliferating cells (proliferating cell nuclear antigen). Transcripts for this gene were detected in a variety of normal and tumor cells, as well as in several human tissues.