Krüppel-like factor family (KLF)

Krüppel-like factors (KLFs) are a family of 18 zinc-finger transcription factors (KLF1 to KLF18) that regulate essential biological processes such as cell proliferation, differentiation, and apoptosis (PMID: 20802471). They are defined by three highly conserved C-terminal C2H2-type zinc finger domains that bind to GC-rich sequences or GT boxes in the promoter regions of target genes (UniProt). KLFs act as transcriptional activators or repressors, often interacting with co-activators like p300 or co-repressors like Sin3A to modulate gene expression (PMID: 31431504). In clinical contexts, KLFs are significant in oncology, where KLF4 can act as either a tumor suppressor or an oncogene depending on the tissue, and KLF5 is frequently overexpressed in epithelial cancers (PMID: 24510068). Beyond cancer, KLF2 and KLF4 are vital for vascular health, mediating the anti-inflammatory and anti-thrombotic effects of laminar shear stress (PMID: 18662921). Therapeutic strategies include small molecule inhibitors like ML264 for KLF5 and inducers like APTO-253 for KLF4, though the structural similarity between family members poses a challenge for selective drug design (PMID: 28811286).

Other names

Krüppel-like factorsBTEB proteinsBasic transcription element-binding proteinsSP1-like transcription factors

KLFs modulate gene expression by binding to GC-rich DNA sequences or GT boxes via their C-terminal C2H2 zinc finger domains, recruiting co-activators or co-repressors to regulate transcription of genes involved in cell cycle and differentiation (PMID: 20802471).