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Updated: Apr 26, 2026

Chromatin Immunoprecipitation ChIP in Mouse T-cell Lines
Published on: June 17, 2017
NACK is an integral component of the Notch transcriptional activation complex and is critical for development and
Kelly L Weaver1, Marie-Clotilde Alves-Guerra2, Ke Jin1
1Molecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida.
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.
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