Figure 3. KLF4 and KLF5 regulate cell proliferation in a context dependent manner.

Generally, KLF4 inhibit cell cycle and KLF5 stimulates proliferation by regulating the transcription of cell cycle genes. But the cytostatic action of KLF4 can be neutralized by CDKN1A (p21) inactivation, the oncogenic RAS^V12 mutation, or cyclin-D1 overexpression (a common target of KLF4 and RAS). The cell cycle regulation function of KLF5 can be switched by the status of p53, which is a frequently inactivated tumor suppressor in cancers and posttranslational modification, especially acetylation. When p53 is mutated or KLF5 is acetylated at Lys369, which can be triggered by the TGF-β signaling, KLF5 becomes anti-proliferative through transactivating CDKN1A (p21) or CDKN2B (p15), respectively.