Cell culture experiments and human cancer tissue suggested that PTEN might be a NEDD4-1 and NEDD4-2 substrate [177,178,179,180,239]), but analysis of NEDD4-1 and NEDD4-2 knockout mice has shown that PTEN stability, subcellular localisation, and activity are not altered in the absence of NEDD4-1 and/or NEDD4-2 [181,182]. Here, PTEN is linked to cancer.