| First Author | Yasuda J | Year | 2004 |
| Journal | Cancer Sci | Volume | 95 |
| Issue | 1 | Pages | 52-7 |
| PubMed ID | 14720327 | Mgi Jnum | J:150924 |
| Mgi Id | MGI:3852311 | Doi | 10.1111/j.1349-7006.2004.tb03170.x |
| Citation | Yasuda J, et al. (2004) Nemo-like kinase suppresses a wide range of transcription factors, including nuclear factor-kappaB. Cancer Sci 95(1):52-7 |
| abstractText | 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. |
