In line with this, mutations in CUL3 significantly co-occur with mutations in TTP53 in HNSCC [119], suggesting that the CUL3-KEAP1 E3 ligase complex may function in concert with deleted, mutated, or degraded TTP53 in HNSCC to promote NFκB, AP-1, and NRF2 activation. This evidence concerns the gene KEAP1 and head and neck squamous cell carcinoma.