Nemo-like kinase suppresses a wide range of transcription factors, including nuclear factor-kappaB.

Nemo-like kinase (NLK) is a serine/threonine kinase that suppresses the transcription activity of the beta-catenin-T-cell factor (TCF) complex through phosphorylation of TCF. Our previous study showed that NLK overexpression induces apoptosis in DLD-1 human colon cancer cells and that apoptosis induction presumably requires a mechanism other than the suppression of ...
beta-catenin-TCF complex. Luciferase reporter gene assay with pNF-kappaB-Luc revealed that NLK could suppress transcription activity of NF-kappaB in a kinase-dependent manner. However, it appeared that transcription co-activators of NF-kappaB, such as CREB binding protein (CBP)/p300, were likely to be the direct targets of NLK, rather than NF-kappaB itself. Luciferase reporter gene analysis of GAL4-CBP fusion proteins revealed that the C-terminal region of CBP was critical for transcription suppression by NLK. In vitro kinase assay showed that NLK could phosphorylate the C-terminal domain of CBP. However, HAT activity was not suppressed by the induction of wild-type NLK in DLD-1 cells. Furthermore, we observed that NLK suppressed the transcription activity of AP-1, Smad, and p53, all of which also utilize CBP as a co-activator. The extent of suppression by NLK was similar among the transcription factors tested (50-60% reduction). Our results suggest that NLK may suppress a wide range of gene expression, possibly through CBP.
Mesh Terms:
CREB-Binding Protein, Cell Line, Tumor, Colonic Neoplasms, Fluorescent Antibody Technique, Gene Expression Regulation, Genes, Reporter, Humans, I-kappa B Kinase, Immunoblotting, NF-kappa B, Nuclear Proteins, Precipitin Tests, Protein-Serine-Threonine Kinases, Trans-Activators, Transcriptional Activation, Transfection
Cancer Sci.
Date: Jan. 01, 2004
Download Curated Data For This Publication
170644
Switch View:
  • Interactions 4