Fibroblast growth factor 23 (FGF23) is a key humoral factor in phosphate homeostasis and skeletogenesis, though the nature of its intracellular signaling is still unclear. Recently, Egr-1, a zinc-finger transcription factor, was identified as an immediate early response gene of FGF23 in the kidney. We report here, that FGF23 induces not only Egr-1 but also two isoforms of NAB2, which are specific co-repressors of Egr-1. Both isoforms of NAB2 induced by FGF23 were localized in the nucleus and suppressed the transcriptional activity of Egr-1. A negative feedback loop established by Egr-1 and NAB2 may thus be involved in mediating the physiological effects of FGF23. (c) 2006 Elsevier Inc. All rights reserved.