A NEW MEMBER OF THE DP FAMILY, DP-3, WITH DISTINCT PROTEIN PRODUCTS SUGGESTS A REGULATORY ROLE FOR ALTERNATIVE SPLICING IN THE CELL-CYCLE TRANSCRIPTION FACTOR DRTF1 E2F/

Integrating cell cycle progression with transcription provides an impo rtant level of control during proliferation, The cellular transcriptio n factor DRTF1/E2F is implicated in this integration process by virtue of its physical interaction and control by key regulators of prolifer ation, such as retinoblastoma protein, cyclins and cyclin-dependent ki nases and regulation of target genes required for cell cycle progressi on, Generic DRTF1/E2F DNA binding activity arises when a member of two distinct families of proteins, DP and E2F, interact as DP/E2F heterod imers, Here, we report the isolation and characterisation of a new mem ber of the murine DP family, called DP-3 (also referred to as human DP -2), In contrast to previously characterised members of the DP and E2F families, processing of DP-3 RNA provides an important level of contr ol by generating at least four distinct DP-3 proteins, of which three have been isolated, called alpha, beta and gamma, Processing events, w hich we show are both tissue- and cell-restricted, can occur either in the 5' region of DP-3 RNA and determine whether translation begins at one or two potential intiating codons, or within the coding sequence, producing variations in internal domains of the DP-3 proteins, The DP -3 proteins studied can co-operate with E2F-1 in DNA binding activity and trans activation of E2F site-dependent transcription, This analysi s of DP-3, which has uncovered a hitherto unexpected and surprising le vel of complexity, documents a new member of the DP family and novel l evels of control which may influence the activity DRTF1/E2F and hence cell cycle progression.