Therefore, further research on the ubiquitination sites of Raf-1 regulated by E3 ligases or USP7 is expected to modulate the ERK1/2 signaling pathway by selectively regulating the stability or activity of Raf-1, which could be a new therapeutic strategy in the ERK1/2 cascade activated cancers (Fig. 6). This evidence concerns the gene MAPK3 and cancer.