Structure and function of the Epstein-Barr virus transcription factor, EBNA 3C

EBNA 3C is one of only nine proteins expressed by the tumourigenic gamma-herpesvirus Epstein-Barr virus (EBV) during the infection and immortalization of human B lymphocytes. In fact, the expression of EBNA 3C has been shown to be essential for the B-cell transformation process to take place. The mechanism by which EBNA 3C contributes to viral pathogenicity has therefore been the subject of intensive research over many years. The first clues on the function of EBNA 3C came from analysis of the primary amino acid sequence of EBNA 3C which identified a number of domains commonly found in transcriptional regulatory proteins. These domains include a proline-rich and a glutamine-proline-rich domain and a putative bZIP domain located in the N-terminus of the protein. EBNA 3C has subsequently been shown to function as a regulator of both viral and cellular transcription and to have potent effects oil normal cell-cycle regulatory pathways. This review will discuss our current knowledge of the functions of EBNA 3C, the roles played by the different domains of EBNA 3C in these Functions, and summarize some recent work from our laboratory that provides the first structural and functional analysis of the putative Mill domain of EBNA 3C.