ASSOCIATION OF THE TLX-2 HOMEODOMAIN AND 14-3-3-ETA SIGNALING PROTEINS

Homeodomain proteins play important roles in various developmental pro cesses, and their functions are modulated by polypeptide cofactors. He re we report that both in vitro and in vivo 14-3-3 eta is associated w ith the TLX-2 homeodomain transcription factor that is required for mo use embryogenesis. Expression of 14-3-3 eta shifts the predominant loc alization of TLX-2 in COS cells from the cytoplasm to the nucleus. Tlx -2 and 14-3-3 eta are expressed in the developing peripheral nervous s ystem with spatially and temporally overlapping patterns, and they are also coexpressed in PC12 cells. Increased expression of either gene b y transfection considerably inhibited nerve growth factor-induced neur ite outgrowth of PC12 cells, and cotransfection of both genes led to a synergistic effect of suppression. These findings define 14-3-3 eta a s a functional modulator of the TLX-2 homeodomain transcription factor and suggest that the in vivo function of TLX-2 in neural differentiat ion is likely regulated by signaling mediated by 14-3-3 eta.