However, the therapeutic effect of LIGHT as a systemic anticancer agent is currently insufficient because of its instability and its binding to nonfunctional soluble decoy receptor 3 (DcR3), which is overexpressed in various tumors.
CID-dependent trapping of enzymes to nonfunctional sites has been established as an elegant approach to interrupt signaling pathways.[ 19, 20] Optically guided cleavage of MeNV-HaXS can release anchored proteins and restore their function.
However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites.
Binding to background sites does not significantly reduce the binding to a specific functional site [ 13].
Based on Lin and Riggs (1975), to compensate for dilution of functional, noncoding DNA, a corresponding increase in regulatory protein in the nucleus would be required in order to fully occupy functional TF binding sites, simultaneously resulting in many more nonfunctional sites.
The two most common are binding to the ligand-binding site of the receptor and, conversely, binding to the receptor-binding site of the ligand.
Such genome-wide studies showed that transcription factors bind to many DNA sites that are apparently nonfunctional in the nuclei.
Furthermore, mLIGHT-Lys was not trapped by the nonfunctional DcR3, despite binding to its functional receptors.
As expected, this change was in opposite directions (supplementary table S6, Supplementary Material online): Expression of MCT1 increased after turning the Reb1p binding site nonfunctional, but decreased after targeting the Ndt80p binding site.
Furthermore, Sst2, while sharing a high level of sequence similarity with AMSH in both its catalytic and MIT (microtubule interacting and trafficking) domain (for binding to ESCRT-III members), bears three substitutions in its corresponding SBM that are presumed to render the SBM nonfunctional for binding to the SH3 domain of STAM (Hse1 in S. pombe).
