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Notch1 Augments Nf- ĸb Activity By Facilitating Its Nuclear Retention, H. M. Shin, Lisa Minter, O.H. Cho, S. Gottipati, A.H. Fauq, T.E. Golde, G.E. Sonenshein, B.A. Osborne

Lisa Minter

Notch1 specifically upregulates expression of the cytokine interferon-gamma in peripheral T cells through activation of NF-kappaB. However, how Notch mediates NF-kappaB activation remains unclear. Here, we examined the temporal relationship between Notch signaling and NF-kappaB induction during T-cell activation. NF-kappaB activation occurs within minutes of T-cell receptor (TCR) engagement and this activation is sustained for at least 48 h following TCR signaling. We used gamma-secretase inhibitor (GSI) to prevent the cleavage and subsequent activation of Notch family members. We demonstrate that GSI blocked the later, sustained NF-kappaB activation, but did not affect the initial activation of NF-kappaB. Using biochemical approaches, …