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. 2005 Aug 19;95(1):52–57. doi: 10.1111/j.1349-7006.2004.tb03170.x

Nemo‐like kinase suppresses a wide range of transcription factors, including nuclear factor‐kB

Jun Yasuda 1, Hideki Yokoo 2, Tesshi Yamada 2, Issay Kitabayashi 3, Takao Sekiya 4,5, Hitoshi Ichikawa 1
PMCID: PMC11158368  PMID: 14720327

Abstract

Nemo‐like kinase (NLK) is a serine/threonine kinase that suppresses the transcription activity of the β‐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 β‐catenin‐TCF complex. Luciferase reporter gene assay with pNF‐kB‐Luc revealed that NLK could suppress transcription activity of NF‐kB in a kinase‐dependent manner. However, it appeared that transcription co‐activators of NF‐kB, such as CREB binding protein (CBP)/p300, were likely to be the direct targets of NLK, rather than NF‐kB 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. (Cancer Sci 2004; 95: 52–57)

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