Thus, our results strongly suggest that the ubiquitination of mutp53 by TRIM21 is a critical mechanism underlying mutp53 regulation in cancer cells, and furthermore, the downregulation of TRIM21 expression, which is frequently observed in some cancers, including colorectal and breast cancers, is an important mechanism contributing to mutp53 accumulation and GOF in cancer (Figure 8). Here, TRIM21 is linked to breast cancer.