Fig. 2. PTMs regulate the activation and carcinogenesis of KRAS.

A series of modifications occur during the activation or inactivation of KRAS. Each known enzyme that is responsible for a particular process is exhibited. KRAS proteins undergo consecutive modifications to assure their attachment to the plasma membrane and subsequent activation. Meanwhile, there are other modifications that regulate their activation and carcinogenic potency. These processes are indicated by three font colors, where red represents anticancer, green denotes pro-cancer, and brown indicates unconfirmed processes. In addition, the consequence of each modification is also depicted by lines with different colors, where the purple line represents the impact on the level of the GTP-bound state, the yellow line indicates the impact on protein stability, and the pink line denotes the impact on interactions with effectors. GEF guanine nucleotide exchange factors, GAP GTPase-activating proteins, FTase farnesyltransferase, NO nitric oxide, PIAS4 protein inhibitor of activated STAT 4, RCE1 RAS-converting enzyme 1, ICMT isoprenylcysteine carboxyl methyltransferase, PKC protein kinase C, APT acyl protein thioesterase, and PAT protein acetyltransferases.