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Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO
13:02

Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO

Published on: December 28, 2019

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

Jun Yasuda1, Hideki Yokoo, Tesshi Yamada

  • 1Cancer Transcriptome Project, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. jyasuda@ncc.go.jp

Cancer Science
|January 15, 2004
PubMed

Insights

Nemo-like kinase (NLK) suppresses gene transcription by targeting co-activators like CREB binding protein (CBP). This kinase activity impacts multiple transcription factors, suggesting a broad role in gene regulation beyond beta-catenin signaling.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Nemo-like kinase (NLK) is a serine/threonine kinase.
  • NLK phosphorylates TCF, suppressing beta-catenin-TCF complex activity.
  • Previous studies linked NLK overexpression to apoptosis in colon cancer cells.

Purpose of the Study:

  • To investigate the mechanism by which NLK suppresses transcription.
  • To determine if NLK directly targets NF-kappaB or its co-activators.
  • To explore NLK's broader role in regulating transcription factors.

Main Methods:

  • Luciferase reporter gene assays (pNF-kappaB-Luc, GAL4-CBP fusion proteins).
  • In vitro kinase assays to assess NLK phosphorylation of CBP.
  • Analysis of NLK's effect on transcription factors AP-1, Smad, and p53.

Main Results:

  • NLK suppresses NF-kappaB transcription activity in a kinase-dependent manner.
  • NLK directly phosphorylates the C-terminal region of CBP/p300.
  • NLK suppresses transcription activity of AP-1, Smad, and p53, which use CBP as a co-activator.

Conclusions:

  • NLK's kinase activity targets transcription co-activators like CBP.
  • NLK broadly suppresses gene expression by interacting with CBP.
  • NLK may regulate diverse cellular processes through CBP-mediated pathways.

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