Furthermore, many mutations in the DNA-binding domain of p53 are shown in human cancers as “hotspot mutations.” Interestingly, in contrast to the DNA-binding domain, the mutations in the C-terminal regulatory domain of p53 still maintain p53’s ability to repress PDCD4 expression, including K368R, S392A, 6KR, and D391AD393A (Figure 5), which suggests that PTMs play a minor role in p53-mediated PDCD4 repression. The gene discussed is PDCD4; the disease is cancer.