However, NRF2 can be ubiquitinated for degradation also by other E3 ligases such as TRIM22, which accelerates the ubiquitination and proteasomal degradation of NRF2 and increases autophagy but independently of KEAP1 activity, as seen in in vitro experiments on osteosarcoma [59]. Here, NFE2L2 is linked to osteosarcoma.