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Regulation of TCF3 Phosphorylation and Function by Wnt Signaling
Dr. Hiroki Hikasa
Department of Developmental and Regenerative Biology
Mount Sinai School of Medicine
U. S .A.
場所:東京大学 理学部2号館 第一講義室(201号室)

要旨:T-cell factor 3 (TCF3) plays key roles in cell fate determination in
vertebrate embryos and embryonic stem cell differentiation and has been
implicated in Wnt signaling. Based on genetic evidence and knockdown
experiments&s_comma; vertebrate TCF3 proteins function largely as transcriptional
repressors&s_comma; although the mechanism of TCF3 regulation and function remains
unclear. A commonly accepted model of Wnt signaling in Drosophila and
mammalian cells involves target gene activation by a complex of a TCF family
member with beta-catenin. Here we demonstrate that Wnt proteins stimulate
rapid phosphorylation of TCF3 in Xenopus gastrulae and mouse embryonic stem
cells. This phosphorylation event is essential for maintaining
ventroposterior fate&s_comma; involves homeodomain-interacting protein kinase 2
(HIPK2) and beta-catenin and leads to the dissociation of TCF3 from the
promoter of Vent2&s_comma; a Wnt target gene with a pivotal role in ventroposterior
development. These results reveal a novel Wnt signaling mechanism operating
to control cell fates in vertebrate embryogenesis.

問合せ先:東大・院理・生物科学 平良眞規 (03-5841-4434)