DNA-binding protein Ikaros (IKZF1) (IKZF1)

DNA-binding protein Ikaros (IKZF1) is a zinc-finger transcription factor that serves as a master regulator of hematopoiesis and lymphoid development (UniProt: P35226). It functions by modulating chromatin structure and regulating the expression of genes essential for B-cell and T-cell specification and maturation (PubMed: 29133302). In the context of disease, IKZF1 deletions or mutations are frequently observed in B-cell acute lymphoblastic leukemia (B-ALL), where they serve as a significant poor prognostic marker (PubMed: 19129520). In multiple myeloma, Ikaros is a key survival factor for plasma cells, making it a primary therapeutic target for immunomodulatory imide drugs (IMiDs) like lenalidomide and pomalidomide (PubMed: 24284190). These drugs function as molecular glues, recruiting Ikaros to the CRL4-CRBN E3 ubiquitin ligase complex for targeted proteasomal degradation, thereby inducing apoptosis in malignant cells (PubMed: 24284191).

Other names

Ikaros family zinc finger protein 1Lymphoid transcription factor IkarosZinc finger protein, subfamily 1A, 1ZNFN1A1LYF1IK1hIk-1

Molecular glue-induced recruitment to the CRL4-CRBN E3 ubiquitin ligase complex, leading to polyubiquitination and subsequent proteasomal degradation (PubMed: 24284190, PubMed: 24284191).