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. 2015 Oct 5;6(33):34342–34357. doi: 10.18632/oncotarget.5326

Figure 9. Schematic model of the cross-talk between LNX2 and WNT/NOTCH pathways.

Figure 9

For clarity, we show the effect of LNX2 on NOTCH pathway with the WNT pathway unaffected. However, NOTCH and WNT pathways have been reported to work cooperatively in tumorigenesis and hence a change in one will affect the other [41]. Based on our studies, LNX2 can bind numb and induce its ubiquitination and subsequent proteasomal degradation [44]. Numb inhibits the NOTCH pathway by degrading NICD [53]. Aberrant changes in the WNT and NOTCH pathways have been associated with cancer [54, 55]. This leads us to speculate a role for LNX2 in tumorigenesis by affecting the WNT and NOTCH pathways through the ubiquitination of Numb. Our study provides the structure of the functional machinery of LNX2 and thus a potential target for therapeutic intervention. Abbreviations: NICD, Notch intracellular domain; Ub, Ubiquitin.