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

Autor:	Weaver KL; Molecular 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., Alves-Guerra MC; Inserm U1016, Institut Cochin, Paris, France. CNRS, UMR 8104, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Jin K; Molecular 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., Wang Z; Molecular 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., Han X; Molecular 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., Ranganathan P; Molecular 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., Zhu X; Molecular 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., DaSilva T; Molecular 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., Liu W; Molecular 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. Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chonqing, China., Ratti F; Ecole Normale Supérieure de Lyon, CNRS UMR 5239, Equipe de Différenciation Neuromusculaire, Lyon, France., Demarest RM; Rowan University School of Osteopathic Medicine, Department of Molecular Biology, Stratford, NJ., Tzimas C; Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Rice M; Molecular 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., Vasquez-Del Carpio R; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Dahmane N; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Robbins DJ; Molecular 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., Capobianco AJ; Molecular 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. tcapobianco@med.miami.edu.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2014 Sep 01; Vol. 74 (17), pp. 4741-51. Date of Electronic Publication: 2014 Jul 18.
DOI:	10.1158/0008-5472.CAN-14-1547
Abstrakt:	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. (©2014 American Association for Cancer Research.)
Databáze:	MEDLINE
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