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. 2013 Jul 11;4:2124. doi: 10.1038/ncomms3124

Figure 5. A cancer drug target revealed by predicted negative genetic interactions.

Figure 5

NSUN2 is predicted to have a negative genetic interaction with FBXW7. Targeting NSUN2 can kill the cancer cells while leaving the normal cell relatively unaffected. In normal cells, the tumour-suppressor gene FBXW7 has functional redundancy with NSUN2 in regulating cellular differentiation. In cancer cells, loss of function of FBXW7 results in an elevated expression of c-Myc. Activation of c-Myc results in the upregulation of NSUN2 that is essential for cell proliferation. Owing to a synthetic lethality between FBXW7 and NSUN2, targeting NSUN2 kills cancer cells, while leaving normal cells relatively unaffacted. A solid line represents an active protein, for example, FBXW7 inhibiting the accumulation of NOTCH1 and NOTCH3 in normals cells45. A red cross illustrates the disruption of the function of a protein, that is, transcriptional regulation of NSUN2 by c-Myc2 is repressed in normal cell, or the disruption of a cellular function, that is, differentiation or proliferation.