DNA-binding protein inhibitor ID-1 (ID1) (ID1)

DNA-binding protein inhibitor ID-1 (ID1) is a member of the inhibitor of DNA binding family, characterized by a helix-loop-helix (HLH) domain but lacking a basic DNA-binding region [1, 11]. It functions as a dominant-negative regulator by heterodimerizing with basic helix-loop-helix (bHLH) transcription factors, such as E-proteins, thereby preventing them from binding to DNA and activating target genes [10, 11]. ID1 plays a critical role in maintaining cell stemness, promoting proliferation, and inhibiting differentiation during development, but its expression is typically silenced in most adult tissues [14, 21]. In various cancers, ID1 is frequently overexpressed and acts as a potent promoter of tumorigenesis, epithelial-mesenchymal transition (EMT), angiogenesis, and metastasis [1, 5, 22]. It is also implicated in drug resistance and poor prognosis across multiple malignancies, including breast, lung, and prostate cancers [1, 14, 28]. Therapeutic strategies targeting ID1 include small-molecule antagonists like AGX51 that induce its degradation, as well as indirect modulation via USP1 inhibitors or natural compounds like cannabidiol [16, 17, 21]. Despite its potential as a target, ID1 has historically been considered "undruggable" due to its lack of a traditional ligand-binding pocket, necessitating innovative approaches to disrupt its protein-protein interactions [17, 21].

Other names

Inhibitor of differentiation 1Inhibitor of DNA binding 1bHLHb24IDHLH protein

Inhibition of ID1 protein-protein interactions with bHLH transcription factors; Induction of ubiquitin-mediated proteasomal degradation of ID1; Transcriptional downregulation of ID1 gene expression; RNA interference-mediated degradation of ID1 mRNA