Aiolos and Ikaros

Aiolos and Ikaros (encoded by the genes IKZF3 and IKZF1, respectively) are members of the Ikaros family of zinc-finger transcription factors, and are responsible for plasmacytoid dendritic cell differentiation and B-cell development.1-3

  • Aiolos is required for the generation of high affinity bone marrow plasma cells,4 and Ikaros is a crucial differentiation factor for plasmacytoid dendritic cells.3
  • Genome-wide association studies have shown that polymorphisms in IKZF3 and IKZF1 correlated with an increased risk for developing systemic lupus erythematosus (SLE)1-4, and Aiolos and Ikaros were overexpressed in the peripheral blood of patients with SLE as compared to healthy controls.1,2,5,6
  • Aiolos and Ikaros are substrates of the cullin ring ligase 4 (CRL4CRBN) E3 ubiquitin ligase complex.7 Cereblon (CRBN) is the target protein receptor on CRL4CRBN.1,8
  • Cereblon (CRBN) may be redirected to induce ubiquitination and subsequent proteasomal degradation of target proteins, including Aiolos and Ikaros.1,2

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References

  1. Schafer PH, Ye Y, Wu L, et al.  Ann Rheum Dis. 2018;77(10):1516-1523.
  2. Nakayama Y, Kosek J, Capone L, et al.  J Immunol. 2017;199(7):2388-2407.
  3. Cytlak U, Resteu A, Bogaert D, et al. Nat Commun. 2018;9(1):1239.
  4. Cortés M, Georgopoulos K. J Exp Med. 2004;199(2):209-219.
  5. Cunninghame Graham DS, Morris DL, Bhangale TR, et al. PLoS Genet. 2011;7(10):e1002341.
  6. Lessard CJ, Adrianto I, Ice JA, et al. Am J Hum Genet. 2012;90(4):648-660.
  7. Gandhi AK, Kang J, Havens CG, et al. Br J Haematol. 2014;164(6):811-821.
  8. Ito T, Ando H, Suzuki T, et al. Science. 2010;327(5971):1345-1350.