Ikaros family zinc finger protein 1 (IKZF1) (IKZF1)

Ikaros family zinc finger protein 1 (IKZF1), also known as Ikaros, is a critical transcription factor involved in the regulation of hematopoiesis and the development of the lymphoid lineage (UniProt Q13422). It functions by binding to DNA and recruiting chromatin remodeling complexes, such as NuRD, to regulate the expression of genes essential for B-cell and T-cell differentiation. In clinical oncology, IKZF1 is recognized as a primary neo-substrate of the Cereblon (CRBN) E3 ubiquitin ligase complex when modulated by immunomodulatory imide drugs (IMiDs) like lenalidomide (Kronke et al., 2014, Science). The binding of these drugs to the thalidomide-binding domain of CRBN alters its surface molecular glue properties, inducing the recruitment, polyubiquitination, and subsequent proteasomal degradation of IKZF1 (Lu et al., 2014, Science). This degradation is particularly lethal to multiple myeloma cells, as it leads to the rapid downregulation of essential survival factors such as IRF4 and MYC. Consequently, IKZF1 is a pivotal therapeutic target in the treatment of various hematologic malignancies, while its genetic loss or mutation is also a hallmark of high-risk B-cell acute lymphoblastic leukemia (Mullighan et al., 2008, Nature).

Other names

IkarosIK1LYF1ZNFN1A1Zinc finger protein IkaroshIK-1

Targeted protein degradation via CRBN-mediated ubiquitination (Molecular glue)