Nature Cell Biology: Deubiquitinating enzyme OTUD3 regulates PTEN stability

PTEN is a tumor suppressor gene that has been found to be frequently mutated in many tumors after p53.

The team led by researcher Zhang Lingqiang of the Academy of Military Medical Sciences discovered that the deubiquitinating enzyme OTUD3 maintains its protein level by removing the polyubiquitination of PTEN and inhibits tumor formation

Unlike p53, which is rapidly degraded, PTEN seems to be a relatively stable protein, indicating that cells maintain protein stability through a certain mechanism

OTUD3 maintains the stability of PTEN

They carried out a screening of deubiquitinating enzyme (DUB) in the whole proteome and found that OTUD3 (OTU domain-containing protein 3) can significantly up-regulate the level of PTEN

Further analysis showed that the N-terminal OTU-containing region of OTUD3 mediates the interaction with the PTEN C2 domain

Knockdown of OTUD3 or PTEN will increase the phosphorylation level of Akt and its downstream targets

OTUD3 inhibits tumor formation in vivo and in vitro

Researchers speculate that OTUD3 may act as a tumor suppressor like PTEN

In order to further study the tumor suppressor effect of OTUD3 in vivo, the researchers commissioned Saiye Biotech to construct a transgenic mouse model of OTUD3

OTUD3 mutations in human cancers

Due to its tumor suppressor properties, researchers speculate that OTUD3 is mutated in human breast cancer

They also found that compared with adjacent tissues, the expression of OTUD3 mRNA in cancer tissues was significantly reduced, and the protein level of PTEN was positively correlated with the expression of OTUD3

In summary, this study determined that OTUD3 is a specific deubiquitinating enzyme that can remove the polyubiquitination modification of PTEN

Original Search

Yuan, L.