DNA-binding protein inhibitor ID-4 (ID4)

DNA-binding protein inhibitor ID-4 (ID4) is a member of the inhibitor of DNA-binding/differentiation (ID) protein family, which act as dominant-negative antagonists of basic helix-loop-helix (bHLH) transcription factors. Unlike other ID family members (ID1–3), ID4 possesses unique tissue- and context-specific biological functions in both development and cancer, sometimes acting as a tumor suppressor and in other settings being oncogenic. ID4 regulates transcription by sequestering specific bHLH proteins via its HLH domain, lacking a basic domain itself, and thus prevents DNA binding of these transcription factors. ID4 is involved in the regulation of cell proliferation, stem cell maintenance, differentiation, angiogenesis, and senescence, and it is commonly dysregulated in various human cancers, either via overexpression or silencing, often through epigenetic mechanisms. Currently, there are no direct drugs targeting ID4, but its roles in cancer and development render it an active area of biomedical research.

Other names

Inhibitor of differentiation 4ID4

Dominant negative inhibition of bHLH transcription factors via HLH domain-mediated heterodimerization, sequestering bHLH proteins and preventing their binding to DNA/promoting or inhibiting transcriptional programs associated with development, stemness, and cancer