TRANSCRIPTIONAL ACTIVATION AND EXPRESSION OF DP TRANSCRIPTION FACTORSDURING CELL-CYCLE AND TPA-INDUCED U937 DIFFERENTIATION

The human DP genes (DP1, DP2) encode a family of transcription factors that regulate cell cycle related events by forming heterodimers with E2F family proteins. E2F-DP heterodimers have been shown to function a s either positive or negative regulators of many growth control genes such as cdc2, cyclin E, RE, DHFR, and E2FI. Their transcriptional acti vity is mainly influenced by physically interacting with the tumor sup pressor protein RE or its family members, p107 and p130, possibly unde r control of phosphorylation. Our previous studies had demonstrated th e presence of multiple transcripts and 3' variations of DP2. In this s tudy, we found that 5' alternative splicing of DP2 also contributes to the complexity of the DP2 mRNA and protein products. DP2 had been sho wn to induce transcription mediated by E2F1, E2F2, and E2F3, and here we report that DP2 can activate human E2F4 and E2F5 as well by using a transient transfection assay. DP1 and DP2 were evenly expressed durin g TPA-induced U937 cell differentiation, but they showed different exp ression patterns during the cell cycle. The expression of E2F1, RE, an d p107 were undetected after 48 h TPA induction, whereas E2F5 and p130 showed little change. p130-E2F is the only E2F activity in differenti ated U937 cells detected by gel mobility shift assay, suggesting that p130-E2F5 plays a role in maintaining cells in a differentiated state in addition to its contribution to the cell cycle regulation.