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Publication : The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD.

First Author  Kopan R Year  1994
Journal  Development Volume  120
Issue  9 Pages  2385-96
PubMed ID  7956819 Mgi Jnum  J:20157
Mgi Id  MGI:68270 Doi  10.1242/dev.120.9.2385
Citation  Kopan R, et al. (1994) The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development 120(9):2385-96
abstractText  We show that Myf-5 and mNotch mRNA are both present in the presomitic mesoderm before muscle cell commitment and before muscle structural gene activation. The failure of presomitic mesoderm to respond to Myf-5 and express myogenic properties implies that there may be a mechanism in presomitic mesoderm to suppress muscle differentiation. Here we show that ectopic expression of the intracellular domain of mNotch (mNotchIC) functions as a constitutively activated repressor of myogenesis both in cultured cells and in frog embryos. Mutagenesis experiments indicate that the target for inactivation by mNotch is the MyoD basic helix-loop-helix domain. mNotchIC contains a nuclear localization signal and localizes to the nucleus. Removal of the nuclear localization signal (NLS) reduces nuclear localization and diminishes the inhibition of myogenesis caused by Myf-5 or MyoD. Additional experiments show that the CDC10/SW16/ankyrin repeats are also necessary for myogenic inhibition.
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