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@ARTICLE{Tares:177188,
      author       = {K. Tares$^*$ and J. O. Ackermann and I. Koch},
      title        = {{T}he canonical and non-canonical {NF}-κ{B} pathways and
                      their crosstalk: {A} comparative study based on {P}etri
                      nets.},
      journal      = {Biosystems},
      volume       = {211},
      issn         = {0303-2647},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2021-02322},
      pages        = {104564},
      year         = {2022},
      note         = {#EA:C070# / 2022 Jan;211:104564},
      abstract     = {NF-κB is a protein complex that occurs in almost all
                      animal cell types. It regulates the cellular immune
                      responses to stimuli in the nucleus. Dysregulation of NF-κB
                      can cause severe diseases like chronic inflammation,
                      autoimmune diseases or cancer. We modeled the two major
                      pathways leading from the external cellular stimulation of
                      the CD40 receptor to the nuclear translocation of NF-κB
                      dimers, the canonical and non-canonical pathway. Based on
                      literature data, we developed two Petri net models
                      describing these pathways. In a third Petri net, we combined
                      the two models, introducing crosstalk specific in
                      CD40L-stimulated B cells. In terms of structural properties,
                      we checked the Petri nets for their consistency and
                      correctness. To explore differences and similarities, we
                      compared structural properties and the simulation behavior
                      of the models. The non-canonical NF-κB pathway exhibited a
                      more diverse regulation than the canonical pathway. Applying
                      in silico knockout analyses, we were able to quantify the
                      relevance of individual biochemical processes. We predicted
                      interrelationships, e.g., between the synthesis of the
                      protein NF-κB-inducing kinase and the processing of the
                      precursor protein p100. The activation of the transcription
                      factors, p50-RelA and p52-RelB, was affected by most of the
                      knockouts. The results of the in silico knockout were in
                      accordance with experimental studies. The Petri net models
                      provide a basis for further analyses and could be extended
                      to include gene expression, additional pathways, molecular
                      processes, and kinetic data.},
      keywords     = {Canonical (Other) / Insilico knockout matrix (Other) /
                      Invariants (Other) / Manatee invariants (Other) / NF-kB
                      pathway (Other) / Non-canonical (Other) / Petri nets
                      (Other)},
      cin          = {C070},
      ddc          = {570},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34688841},
      doi          = {10.1016/j.biosystems.2021.104564},
      url          = {https://inrepo02.dkfz.de/record/177188},
}