Krüppel-like factor 4 (KLF4) (KLF4)

Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that serves as a master regulator of cell fate, including proliferation, differentiation, and survival [UniProt: P22232]. In the immune system, KLF4 is essential for the transcriptional program that governs CD8+ T cell differentiation, specifically promoting the formation of long-lived memory T cells and preventing terminal exhaustion [PubMed: 29724784]. It achieves this by regulating the expression of key transcription factors like TCF1 and surface markers such as CD62L and CCR7 [PubMed: 32103171]. Beyond immunology, KLF4 is famously known as one of the Yamanaka factors used to reprogram somatic cells into induced pluripotent stem cells (iPSCs) [PubMed: 16904174]. In clinical contexts, KLF4 acts as a context-dependent rheostat, functioning as a tumor suppressor in certain tissues and an oncogene in others [PubMed: 24501217]. Therapeutic targeting of KLF4 is currently explored through small molecules like APTO-253, which induces KLF4 expression to trigger cell cycle arrest and apoptosis in hematologic malignancies [ClinicalTrials.gov: NCT02267863]. However, targeting KLF4 presents significant challenges due to its broad expression and potential to induce cellular dedifferentiation or tumorigenesis if not precisely controlled.

Other names

Gut-enriched Krüppel-like factorGKLFEpithelial zinc finger protein EZF

KLF4 acts as a transcriptional regulator that binds to specific DNA motifs (5'-CACCC-3') to either activate or repress gene expression, thereby controlling cellular processes such as the memory T cell program [PubMed: 29724784, UniProt: P22232].