FGF23 induces expression of two isoforms of NAB2, which are corepressors of Egr-1.
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.
Fukuda
Toru
T
Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Yamane 1397-1, Hidaka-shi, Saitama 350-1241, Japan.
Kanomata
Kazuhiro
K
Nojima
Junya
J
Urakawa
Itaru
I
Suzawa
Tetsuo
T
Imada
Mana
M
Kukita
Akiko
A
Kamijo
Ryutaro
R
Yamashita
Takeyoshi
T
Katagiri
Takenobu
T
D000818:Animals; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; C491000:NAB2 protein, human; D020033:Protein Isoforms; D012097:Repressor Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23