Skip to main content
. 2014 Jul 3;3(7):e941742. doi: 10.4161/21624011.2014.941742

Figure 1.

Figure 1.

Lenalidomide mode of action. The transcription factors IKZF1 and IKZF3 activate transcription of IRF4 which is a transcriptional activator of c-MYC. IKZF1, IKZF3, IRF4 and MYC form a transcriptional network that is essential for multiple myeloma survival and growth. On the IL-2 gene locus IKZF1 and IKZF3 are transcriptional repressors. Lenalidomide promotes ubiquitination of IKZF1 and IKZF3 by the CRBN-CRL4 E3 ligase resulting in their proteasomal degradation. As a consequence of IKZF1 and IKZF3 degradation, IRF4 and MYC transcription decrease resulting in growth inhibition of multiple myeloma cells and de-repression of IL-2 in T cells. Abbreviations: IKZF1 and 3, IKAROS family zinc finger 1 and 3; IL-2, interleukin-2; IRF4, interferon regulatory factor 4.