Principles of Cell Signaling and Biological Consequences
Student #6 Response to Student #14
20 May 2005
IkB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important for the synthesis of immune effector molecules in innate immune responses against lipopolysaccharide and peptidoglycan. It has been shown that NF-kB can negatively regulate Jnk pathways in both mammalian and drosophilia models[1-3]. However, it is not known if similar crosstalk occurs in the opposite direction: Can Jnk negatively regulates the activities of NF-kB signaling modules? In this article, the authors, using a combination of microarray analysis, siRNA and ChIPs assay, demonstrated that crosstalk between drosophilia Jnk and IKK pathways at the junction of AP1, involving histone aceytlation and chromatin remodeling, led to a downregulation of their activities. This article provided evidence of a bidirectional crosstalk and a novel mechanism – involvement of histone aceytlation and chromatin remodeling, that results in a negative regulation of the pathways involved.
I agree with the comments of Student #14 in that this paper is particularly interesting as the crosstalk involves histone acetylation and chromatin remodeling, and the interaction between the two pathways is of great importance for normal physiological responses.
2. Park, J.M., et al., Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila. Genes Dev, 2004. 18(5): p. 584-94.[PubMed] [Full Text in Virtual Journal] [Online Journal]
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