NACK is an integral component of the notch transcriptional activation complex and is critical for development and tumorigenesis

Kelly L. Weaver, Marie Clotilde Alves-Guerra, Ke Jin, Zhiqiang Wang, Xiaoqing Han, Prathibha Ranganathan, Xiaoxia Zhu, Thiago DaSilva, Wei Liu, Francesca Ratti, Renee M. Demarest, Cristos Tzimas, Meghan Rice, Rodrigo Vasquez-Del Carpio, Nadia Dahmane, David J. Robbins, Anthony J. Capobianco

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13 Scopus citations

Abstract

The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are coexpressed during mouse development and that homozygous loss of NACK is embryonic lethal. Finally, we show that NACK is also a Notch target gene, establishing a feed-forward loop. Thus, our data indicate that NACK is a key component of the Notch transcriptional complex and is an essential regulator of Notch-mediated tumorigenesis and development.

Original languageEnglish (US)
Pages (from-to)4741-4751
Number of pages11
JournalCancer Research
Volume74
Issue number17
DOIs
StatePublished - Sep 1 2014

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Weaver, K. L., Alves-Guerra, M. C., Jin, K., Wang, Z., Han, X., Ranganathan, P., Zhu, X., DaSilva, T., Liu, W., Ratti, F., Demarest, R. M., Tzimas, C., Rice, M., Vasquez-Del Carpio, R., Dahmane, N., Robbins, D. J., & Capobianco, A. J. (2014). NACK is an integral component of the notch transcriptional activation complex and is critical for development and tumorigenesis. Cancer Research, 74(17), 4741-4751. https://doi.org/10.1158/0008-5472.CAN-14-1547