Fig. 3

Mechanisms involved in KPC1-dependent impaired tumor growth. KPC1 ubiquitin ligase interacts with the ARs domain of p105 via its 7-aa stretch (WILVRLW). Following ubiquitination, the p105 precursor is processed by the 26S proteasome to generate the p50 active subunit. p50 forms homo- (with p50) or hetero (with p65, the ‘canonical’ NF-κB)-dimers, that move to the nucleus to initiate different transcriptional programs, depending on the composition of the dimers. Excess of p50 probably forms homo-dimers that stimulate: (i) the expression of an array of tumor suppressors and (ii) the expression and secretion of cytokines CCL3, CCL4, and CCL5 that attract the host’s NK cells and macrophages into the tumor, restricting its growth. Also, it inhibits expression of PD-L1 in different tumor cell lines, consequently inhibiting tumor growth