The transcription factor DRTF1/E2F plays a crucial role in regulating cell-cycle progression. In one hand, many of the genes activated at the G1/S transition contain binding sites for this transcription factor and in several cases these sequences are necessary for periodic expression. In the other hand, molecules that regulate cell-cycle progression negatively, such as pRb and related proteins, and positively, such as cyclins and cdks, are able to regulate its activity.
Transcription factor called DRTF1/E2F results from the interaction of two families of proteins, E2F and DP. The interaction is synergistic with respect to both DNA binding and E2F site-dependent transactivation. A recently defined member of the DP family, DP-3, encodes different isoforms which arise by differential processing of the DP-3 mRNA in the coding sequence, together with processing events which occur in the 5' untranslated region. No functional role has been described for these regions, although it is possible that they are involved in the translational regulation of the DP-3 isoforms.
The research proposed in this application aims to assess if the variation in the 5' untranslated region regulates translation. The molecular details of control will be addressed, and the functional physiological implications for DRTF1/E2F activity during cell cycle evaluated.