Inhibition of TAK1 by kamebakaurin in dendritic cells.

Abstract

Kamebakaurin (KA) has anti-cancer and anti-inflammatory activities through direct inhibition of DNA-binding activity of nuclear factor-kappa B (NF-κB) p50. We suggest here another molecular target of KA by the use of lipopolysaccharide-treated dendritic cells. In cell- and enzyme-based assays, KA directly inhibited autophosphorylation and kinase activity of TAK1, followed by the inhibition of TAK1-downstream signaling cascades, such as IKK phosphorylation-IκBα degradation-nuclear translocation of NF-κB, phosphorylation of MEK3/6-p38 mitogen activated protein kinase (MAPK), and MKK4/7-c-Jun N-terminal kinase MAPK. These results demonstrated that TAK1 might be the direct molecular target of KA.

• Authors: Jee Youn Kim, Hyung Sook Kim, Yeon Jin Kim, Hong Kyung Lee, Ji Sung Kim, Jong Soon Kang, Jin Tae Hong, Youngsoo Kim, Bang Yeon Hwang, Sang-Bae Han
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 15 Issue 1 Pg. 138-43 (Jan 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 23159603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Diterpenes
• NF-kappa B
• Recombinant Fusion Proteins
• Nitric Oxide
• kamebakaurin
• Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cytokines (metabolism)
• Dendritic Cells (drug effects, metabolism)
• Diterpenes (pharmacology)
• Female
• MAP Kinase Kinase Kinases (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• NF-kappa B (antagonists & inhibitors)
• Nitric Oxide (metabolism)
• Recombinant Fusion Proteins (metabolism)