Supplementary Figure 11: OTUD3 and USP13 exhibit a synergy effect on PTEN expression in breast cancer samples.
From: Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis
a,b, Potential synergy between OTUD3 and USP13 for PTEN protein levels. Serial sections of tissue arrays 68 patient breast specimens were subjected to immunohistochemistry with anti-OTUD3, anti-USP13 and anti-PTEN antibodies, respectively, and visualized by the DAB staining before imaging. Scale bar represents 50 μm. Representative images were shown in (a), and the summary of the IHC results was listed in (b). P < 0.001, calculated by both Chi-square and χ2 test. Scale bar, 50 μm. c, Regression analysis comparing HAUSP and PTEN expression in breast cancer tissues. n = 37. d, Proposed working model of OTUD3 on PTEN stability control. PTEN is a phosphatase that catalyses the conversion of the lipid second messenger PtdIns(3,4,5)P3 to PtdIns(4,5)P2 and inhibits PI3K-Akt signaling. PTEN protein is relatively stable. This study identifies the deubiquitinase OTUD3 catalyses the removal of poly-ubiquitin chain of PTEN in the cytoplasm. OTUD3 reverses the poly-ubiquitination of PTEN by E3 ubiquitin ligases (such as Nedd4-1, WWP2, XIAP and CHIP) and prevents PTEN degradation by 26S proteasome. On the other hand, a previous study (ref. 22) identified that the deubiquitinase HAUSP is mainly localized in the nucleus and catalyses the removal of mono-ubiquitination of PTEN. HAUSP regulates the PTEN cytoplasm-nucleus shuttling but has no effects on PTEN stability.
