Zinc finger protein Aiolos (IKZF3) (IKZF3)

Zinc finger protein Aiolos, encoded by the IKZF3 gene, is a transcription factor and a critical member of the Ikaros family that regulates lymphocyte development and differentiation, particularly in B-lineage cells and Th17 cells [1, 5]. It functions by binding to specific DNA sequences to modulate gene expression, playing a vital role in B-cell maturation and the suppression of interleukin-2 (IL-2) production in T-cells [3, 5]. In clinical pathology, Aiolos is frequently overexpressed in hematologic malignancies such as multiple myeloma and chronic lymphocytic leukemia (CLL), where it promotes tumor cell survival and resistance to therapy [4, 6]. Beyond oncology, it is also implicated in the pathogenesis of autoimmune disorders like systemic lupus erythematosus (SLE) due to its role in regulating antibody-producing cells [2]. Aiolos is a primary therapeutic target for immunomodulatory imide drugs (IMiDs) and next-generation cereblon E3 ligase modulators (CELMoDs) [7, 8]. These small molecules act as molecular glues that facilitate a physical interaction between Aiolos and the Cereblon (CRBN) component of the CRL4-CRBN E3 ubiquitin ligase complex [8, 9]. This recruitment leads to the polyubiquitination and subsequent proteasomal degradation of Aiolos, which in turn causes the downregulation of essential oncogenic transcription factors like IRF4 and MYC, ultimately inducing apoptosis in malignant plasma cells [3, 9]. Citations: [1] UniProt Q9UKT9; [2] PubMed 24451536; [3] PubMed 24403012; [4] PubMed 23836551; [5] NIH Gene ID 22806; [6] PubMed 23423580; [7] DrugBank DB15254; [8] PubMed 24292623; [9] PubMed 35914151.

Other names

AiolosIKZF3DNA-binding protein AiolosIkaros family zinc finger protein 3Zinc finger protein 1, subfamily A, 3ZNFN1A3

Targeted protein degradation via recruitment to the CRL4-CRBN E3 ubiquitin ligase complex (molecular glue mechanism).