Ikaros zinc finger protein 1 (IKZF1) and Ikaros zinc finger protein 3 (IKZF3) (IKZF1 (Ikaros), IKZF3 (Aiolos))

Ikaros zinc finger protein 1 (IKZF1) and Ikaros zinc finger protein 3 (IKZF3) are zinc finger transcription factors that play essential roles in hematopoiesis and immune cell development, particularly in B and T lymphocyte lineages[1][3][4]. Both proteins are part of the Ikaros family, characterized by N-terminal zinc finger domains for DNA binding and C-terminal zinc finger domains for protein-protein interactions, enabling dimerization and complex formation[3][4]. IKZF1 (Ikaros) acts as a master regulator of lymphoid lineage specification, while IKZF3 (Aiolos) modulates more mature phases of lymphocyte function. Genetic alterations in IKZF1 are strongly associated with chemotherapy resistance and adverse outcomes in B-cell acute lymphoblastic leukemia[1]. Both IKZF1 and IKZF3 are critical therapeutic targets in hematologic malignancies such as multiple myeloma, where drugs like lenalidomide induce their degradation to exert anti-tumor effects[2][4]. These proteins also participate in chromatin remodeling and gene regulation complexes, further influencing cell proliferation, differentiation, and apoptosis[1][3][7].

Other names

IkarosDNA-binding protein IkarosAiolosIkaros family zinc finger proteinsIkZF family transcription factors

Drugs such as lenalidomide and pomalidomide bind to the E3 ubiquitin ligase substrate receptor cereblon, which induces ubiquitination and proteasomal degradation of IKZF1 and IKZF3 in multiple myeloma cells, leading to decreased survival of malignant cells[2][4].