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. 2022 Nov 16;54(11):1814–1821. doi: 10.1038/s12276-022-00887-w

Fig. 3. Proposed model showing the mechanisms of DUB action for PTEN.

Fig. 3

While HAUSP/USP7 induces deubiquitination and subsequent nuclear exclusion of monoubiquitinated PTEN in the nucleus, where it can control the cell cycle and genomic stability, PML-RARα, NPMc+, and BCR-ABL promote HAUSP-mediated PTEN deubiquitination in blood-borne cancers. USP11 plays a role in the maintenance of the effective levels of both nuclear and cytosolic PTEN for tumor suppression, and interestingly, its expression and activity are regulated by the PTEN/PI3K pathway. Furthermore, in the cytoplasm, USP11, USP13, and (acetylated) OTUD3 catalyze the removal of the K48-linked polyubiquitin chain on PTEN to enhance protein stability, whereas USP10 recognizes and removes the K63-linked polyubiquitin chain from PTEN, leading to PTEN recruitment to the plasma membrane. Ataxin-3 represses PTEN by inhibiting its transcription. PTEN phosphatase and tensin homolog deleted on chromosome 10, HAUSP herpesvirus-associated ubiquitin-specific protease, USP10 ubiquitin-specific protease 10, USP11 ubiquitin-specific protease 11, USP13 ubiquitin-specific protease 13, OTUD3 OTU deubiquitinase 3, PI3K phosphoinositide 3-kinase, PIP2 phosphoinositide-4,5-biphosphate, PIP3 phosphoinositide-3,4,5-triphosphate, mTOR mammalian target of rapamycin, PML promyelocytic leukemia, NPMc+ cytoplasmic nucleophosmin, TRIP13 thyroid hormone receptor-interacting protein 13.