Table 4 Proteins regulating cellular clearance - dysregulated by viral invasion

As subunits of NF-κB the homodimers of p65, p50 and p52 (non-Rel-dimers) are, in general, repressors of κB transmission. Homodimers with a RelA, RelB or c-Rel-domain (Rel-dimers) and an additional transactivation domain function as activators of NF-κB related transcription after heterodimerization with non-Rel-dimers. Practically heterodimerization between all the homodimers is possible. But only heterodimers composed of non-Rel- and Rel-dimers have transcription activating function.

Inhibitors, called IκBs (Inhibitors of κB), sequester the NF-κB homodimers in the cytoplasm of unstimulated cells. They do so by using multiple copies of a sequence called ankyrin repeats. By virtue of the ankyrin repeat domains, the IκB proteins mask the nuclear localization signals (NLS) of homodimeric NF- κB proteins. Thus, nuclear translocation of NF-κB dimers is prevented keeping them sequestered in an inactive state in the cytoplasm.

Proteasomes are large (1700 kDa) cytosolic protein complexes which degrade unneeded or damaged proteins by proteolysis which is a key function in cellular homeostasis and survival. To allow proteolytic degradation, the target proteins are tagged with small (8,5 kDa) proteins called ubiquitins. This tagging is catalyzed by enzymes called ubiquitin ligases. In the case of IκBs the viral induced IκB kinase complex (IKK) functions as ubiquitin ligase promoting cleavage of IκB- NF-κB-homodimercomplexes thus, allowing nuclear translocation of NF-κB subunits to form NF-κB.