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Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells
Author(s) -
Kei Sakamoto,
Yoshihiro Tamamura,
Kenichi Katsube,
Akira Yamaguchi
Publication year - 2008
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.023119
Subject(s) - hes1 , biology , notch signaling pathway , transactivation , microbiology and biotechnology , mesenchymal stem cell , runx2 , coactivator , cellular differentiation , lim domain , signal transduction , transcription factor , zinc finger , gene , genetics
Notch signaling is required for multiple aspects of tissue and cell differentiation. In this study, we identified zinc finger protein 64 (Zfp64) as a novel coactivator of Notch1. Zfp64 is associated with the intracellular domain of Notch1, recruited to the promoters of the Notch target genes Hes1 and Hey1, and transactivates them. Zfp64 expression is under the control of Runx2, and is upregulated by direct transactivation of its promoter. Zfp64 suppresses the myogenic differentiation of C2C12 cells and promotes their osteoblastic differentiation. Our data demonstrate two functions of Zfp64: (1) it is a downstream target of Runx2 and, (2) its cognate protein acts as a coactivator of Notch1, which suggests that Zfp64 mediates mesenchymal cell differentiation by modulating Notch signaling.

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