The Notch signal pathway plays important roles in proliferation, apoptosis, and differentiation. Abnormalities in Notch signaling are linked to many human diseases. After ligand binding, Notch signaling is activated through the cleavage of Notch receptors to release and translocate the Notch intracellular domain into the nucleus. The Notch1 receptor intracellular domain (N1IC), the activated form of the Notch1 receptor, can modulate downstream target genes via C promoter-binding factor 1-dependent and -independent pathways. To further dissect the Notch1 signaling pathway, we screened the N1IC-associated proteins using a yeast two-hybrid system and identified nuclear βII- tubulin as a candidate for the N1IC-associated proteins. It was suggested that the presence of βII-tubulin in nuclei might be correlated with the cancerous state of cells. However, the function of βII- tubulin locating in the nucleus still is unknown. Herein, we show that the complex of α- and βII-tubulin is associated with N1IC in cancer cells by a coimmunoprecipitation analysis. The ankyrin domain of the Notch1 receptor alone was sufficient to associate with βII- tubulin. Furthermore, α- and βII-tubulin were localized in the nucleus and formed a complex with N1IC. Treatment with Taxol increased the amounts of nuclear α- and αII-tubulin in K562 and HeLa cells and promoted the C promoter-binding factor 1-dependent transactivation activity of N1IC. We also show that nuclear βII-tubulin was bound on the C promoter-binding factor 1 response elements via the association with N1IC. These results suggest that nuclear βII-tubulin can modulate Notch signaling through interaction with N1IC in cancer cells.

Original languageEnglish
Pages (from-to)8334-8340
Number of pages7
JournalCancer Research
Issue number22
Publication statusPublished - Nov 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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