Wnt signaling directs cell-fate choices during embryonic development and tissue tumorigenesis. T cell fac-tor 4 (TCF4) plays a pivotal role in the Wnt signaling path-way. We demonstrate that a specific protein-protein interac-tion occurs between TCF4 and ATF5 (activating transcrip-tion factor 5) —— a new member of cAMP response element binding protein (CREB) with the yeast two-hybrid system. The N-terminal and DNA binding domain of TCF4 (TCF4ND, 1—495 aa) and the C-terminal spanning bZIP domain of ATF5 (162—282 aa) were found to be responsible for the interaction, and the C-terminal of ATF5 (ATF5/C) showed a much stronger interaction with TCF4ND than the full-length of ATF5 by detecting the b-gal activity. Further-more, overexpression of ATF5/C enhanced transcriptional activation by TCF4 proteins in luciferase assay by transient transfection. Taken together, these data suggest that ATF5 may function as a co-activator to potentiate the ability of TCF4 to activate transcription.
