HAUSP is mainly localized in the nucleus and specifically removes the mono-ubiquitination of PTEN to affect its nuclear exclusion17, while USP13 and OTUD3, which predominantly reside in the cytoplasm or the plasma membrane, reverse the poly-ubiquitination of cytosolic or membrane-bound PTEN protein in a breast cancer-specific context19,20. This evidence concerns the gene OTUD3 and breast carcinoma.