The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia Academic Article uri icon

Overview

MeSH Major

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Leukemia, T-Cell
  • NF-kappa B
  • Receptors, Notch
  • Tumor Suppressor Proteins

abstract

  • It was previously shown that the NF-κB pathway is downstream of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL). Here, we visualize Notch-induced NF-κB activation using both human T-ALL cell lines and animal models. We demonstrate that Hes1, a canonical Notch target and transcriptional repressor, is responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by repressing the deubiquitinase CYLD, a negative IKK complex regulator. CYLD expression was found to be significantly suppressed in primary T-ALL. Finally, we demonstrate that IKK inhibition is a promising option for the targeted therapy of T-ALL as specific suppression of IKK expression and function affected both the survival of human T-ALL cells and the maintenance of the disease in vivo.

publication date

  • January 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2963042

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2010.08.006

PubMed ID

  • 20832754

Additional Document Info

start page

  • 268

end page

  • 81

volume

  • 18

number

  • 3