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Journal of Cell Science 115, 1295-1303 (2002)
© 2002 The Company of Biologists Limited

Research Article

p65-NF{kappa}B synergizes with Notch to activate transcription by triggering cytoplasmic translocation of the nuclear receptor corepressor N-CoR

Lluís Espinosa, Sara Santos, Julia Inglés-Esteve, Pura Muñoz-Canoves and Anna Bigas*

Centre Oncologia Molecular, Institut de Recerca Oncologica, Hospitalet, Barcelona 08907, Spain

* Author for correspondence (e-mail: abigas{at}iro.es )

Accepted 13 December 2001

Notch/RBP-J{kappa} and nuclear factor-{kappa}B (NF{kappa}B) complexes are key mediators of the progression of many cellular events through the activation of specific target gene transcription. Independent observations have shown that activation of Notch-dependent transcription generally correlates with inhibition of differentiation. In contrast, activated NF{kappa}B complexes are required for progression of differentiation in several systems. Although some interactions between both pathways have been observed, the physiological significance of their connection is unclear. We have now demonstrated that the increase in p65-NF{kappa}B protein levels enhances Notch-mediated activation of the Hes1 promoter up to three-fold. This effect does not require NF{kappa}B transcriptional activity, and it is independent of the previously described interaction between Notch and p50-NF{kappa}B. Furthermore, we show that p65-NF{kappa}B can modulate subcellular localization of the transcriptional corepressor N-CoR, abrogating N-CoR mediated repression of the Hes1 promoter. In addition, p65-NF{kappa}B is able to upregulate not only the Hes1 but also other promoters containing SRE and AP-1 sites, which are repressed by N-CoR. Thus, we conclude that p65-NF{kappa}B can regulate gene expression by a general mechanism that involves cytoplasmic translocation of the transcriptional corepressor protein N-CoR.

Key words: NF{kappa}B, N-CoR, Notch, Transcriptional regulation




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