THE ZINC-FINGER TRANSCRIPTION FACTOR ZIF268/EGR-1 IS ESSENTIAL FOR SCHWANN-CELL EXPRESSION OF THE P75 NGF RECEPTOR

Nerve injury alters the function of Schwann cells from quiescent, myelin forming cells to proliferating cells that facilitate nerve repair. The transcription factor, Zif268, may be involved in transmitting injury-related signals since its expression is rapidly induced by nerve transection in vivo and without intervening protein synthesis by injury-related signals in vitro. Expression of the low-affinity p75 nerve growth factor receptor (NGFR(p75)) by Schwann cells after nerve injury closely correlated with the zif268 expression profile, and Zif268 transactivated the NGFR(p75) promoter in transient transfection assays. Conversely, the NGFR(p75) gene was not expressed when Zif268 protein was depleted by stable transfection of antisense cDNA. Moreover, nuclear proteins corresponding to Zif268 bound to the NGFR(p75) promoter by Southwestern blotting, indicating that a direct interaction of Zif268 with the NGFR gene is required for its expression in Schwann cells.