Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene. However, we describe constitutively active forms of Notch1, which inhibit muscle cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent the expression of muscle cell specific genes do not involve the upregulation of endogenous HES-1. In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by which Notch inhibits differentiation. We therefore propose that Notch signaling activates at least two different pathways: one which involves CBF1 as an intermediate and one which does not.
Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway
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C. Shawber, D. Nofziger, J.J. Hsieh, C. Lindsell, O. Bogler, D. Hayward, G. Weinmaster; Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway. Development 1 December 1996; 122 (12): 3765–3773. doi: https://doi.org/10.1242/dev.122.12.3765
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