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.
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
Soumen
S
Basak
Alexander
A
Hoffmann
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