Crosstalk via the NF-kappaB signaling system.
The nuclear factor kappaB (NF-kappaB) family of transcription factors consists of 15 possible dimers whose activity is controlled by a family of inhibitor proteins, known as IkappaBs. A variety of cellular stimuli, many of them transduced by members of the tumor necrosis factor receptor (TNFR) superfamily, induce degradation of IkappaBs to activate an overlapping subset of NF-kappaB dimers. However, generation and stimulus-responsive activation of NF-kappaB dimers are intimately linked via various cross-regulatory mechanisms that allow crosstalk between different signaling pathways through the NF-kappaB signaling system. In this review, we summarize these mechanisms and discuss physiological and pathological consequences of crosstalk between apparently distinct inflammatory and developmental signals. We argue that a systems approach will be valuable for understanding questions of specificity and emergent properties of highly networked cellular signaling systems.
Basak
Soumen
S
Department of Chemistry and Biochemistry, Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States. sobasak@ucsd.edu
Hoffmann
Alexander
A
D000818:Animals; D048788:Growth and Development; D007109:Immunity; D007249:Inflammation / Q000378:metabolism; D008221:Lymphoid Tissue / Q000196:embryology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D018124:Receptors, Tumor Necrosis Factor; D051996:Transcription Factor RelA