WWP2, an E3 ubiquitin ligase, ubiquitinates NOTCH3 cleavage fragments NEXT3 and NICD3 in the cytosol, targeting them for lysosome-mediated degradation. WWP2 thus negatively regulates NOTCH3 signaling. WWP2 is a putative tumor suppressor whose deletions have been reported in the majority of ovarian carcinomas (Jung et al. 2014).
ubiquitin protein ligase activity of NEXT3,NICD3:WWP2 [cytosol]