PMC:1481596 / 21199-22677 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1481596","sourcedb":"PMC","sourceid":"1481596","source_url":"https://www.ncbi.nlm.nih.gov/pmc/1481596","text":"To illustrate the power of COD in elucidating the dynamics behind protein complexes, we consider the TNFα/NF-κB signaling pathway. The Nuclear Factor κB (NF-κB) family of transcription factors is activated in response to a diverse set of stress stimuli, which includes pro-inflammatory cytokines, e.g., TNFα. In vertebrates, this family includes p50, p52, Rel A, c-Rel, and Rel B, which bind to the DNA in a homo or heterodimeric fashion. The NF-κB activity is regulated by the IκB family of proteins via inhibitory ankyrin repeat domains. This family includes IκBα, IκBβ, and IκB∈. The precursors of p50 (p105) and p52 (pl00) also possess ankyrin repeat domains and thus act as inhibitors. These precursors can also form dimers with other members of the NF-κB family. The activation with the pro-inflammatory cytokine tumor necrosis factor TNFα triggers a signaling cascade, which, in particular, stimulates the activation of the IKKα, IKKβ, and IKKγ functional groups. The IKKs initiate a signal induced degradation of the inhibitors (IκBs), and subsequent nuclear translocation of the transcription factor. Recent TAP experiments [5] provide a wealth of new information regarding this important signaling pathway. Bouwmeester et al. identified 221 molecular associations, out of which only 80 where previously known. Gagneur et al. [16] applied modular decomposition to the network of these associations but the decomposition halted quickly at large non-decomposable modules.","tracks":[{"project":"2_test","denotations":[{"id":"16722537-14743216-1694489","span":{"begin":1134,"end":1135},"obj":"14743216"},{"id":"16722537-15287979-1694490","span":{"begin":1336,"end":1338},"obj":"15287979"}],"attributes":[{"subj":"16722537-14743216-1694489","pred":"source","obj":"2_test"},{"subj":"16722537-15287979-1694490","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93afec","default":true}]}]}}