Preferentially expressed antigen of melanoma (PRAME) was first isolated as a human melanoma antigen by cDNA expression cloning using melanoma-reactive cytotoxic Tcells (CTL). PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies and solid tumors, including melanomas, sarcomas, head and neck cancers, small-cell lung carcinomas and renal cell cancers. In normal tissues, PRAME expression has been reported in testis and low levels are found in endometrium, ovaries and adrenals [, , , ]. However, the PRAME gene is also expressed, although at a lower intensity, in CD34+ stem cells from healthy donors, which might constitute a problem for its application as a target in tumor immunotherapy []. Epigenetic events represent the main mechanism regulating the expression of PRAME including DNA methylation of several promoter regions [, ]. Members of the PRAME gene family encode leucine-rich repeat (LRR) proteins functioning as transcription regulators in cancer cells, and are thought to possess roles in spermatogenesis and oogenesis [, ].
This entry represents the CTAG/Pcc1 family. Its members include yeast EKC/KEOPS complex subunit Pcc1, mammalian EKC/KEOPS complex subunit Lage3 and human cancer/testis antigen (CTAG) 1/2. In Saccharomyces cerevisiae, Pcc1 is a component of the EKC/KEOPS protein complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t6A37) in tRNAs that read codons beginning with adenine [].Similar to its S. cerevisiae homologue, human Lage3 is part of the EKC complex that is essential for a universal tRNA modification. The human EKC complex interacts with tumour antigen PRAME (preferentially expressed antigen in melanoma), and hence involved in oncogenesis []. Human CTAG 1 and 2 (also known as NY-ESO-1 and 2) share protein sequence similarity with Pcc1, however, their function is not clear. They are linked to cancer progression [].
