Fig. 6.

A graphical scheme describing the mechanism of tumor suppression by the ubiquitin ligase KPC1. Overexpressed KPC1 (Right) stimulates the limited processing of the NF-ĸB p105 inactive and long precursor to yield excess of the p50 subunit of the mature dimeric transcriptional regulator. In the absence of stoichiometrically available partner—typically p65—p50 probably homodimerizes. Along with an as yet unidentified additional subunit that contains a transactivation domain (X), it suppresses the expression of PD-L1 and stimulates the expression of a set of chemokines. This in turn attracts to the tumor activated NK cells and macrophages. Along with stimulation of expression of tumor suppressors (22), the overall effect of overexpressed KPC1 is strong tumor suppression.