Here, we propose a model for the MAD2L2‐regulated NCOA3 phosphorylation, ubiquitination, and degradation in CRC cells (Fig. 6F): In response to the increased DNA damage and chromosome instability in CRC cells, MAD2L2 had elevated expression and activated p38, which then phosphorylated NCOA3 for subsequent degradation through the ubiquitin–proteasome pathway. Here, NCOA3 is linked to colorectal carcinoma.