Two Studies Suggest New Cancer Treatment Path

A pair of studies conducted by the Memorial Sloan-Kettering Cancer Center have uncovered a regulatory mechanism for the PTEN gene, a commonly mutated tumor suppressor gene. The regulator, NEDD4-1, controls protein stability in cells, and is found in both the cytoplasm and the nucleus.

The first study found that NEDD4-1 is a key component in eliminating PTEN from cells by adding a molecular tag, ubiquitin, to PTEN causing degradation in the cellular machinery called proteasome. The second study found that the ubiquitination of PTEN by NEDD4-1 also regulates another important aspect of PTEN, its cellular localization.

Both studies showed that the PTEN mutation in patients prevented the addition of ubiquitin by NEDD4-1, providing a molecular mechanism for the detrimental effect of the mutant PTEN protein. They showed that the single ubiquitin tagging is necessary to import PTEN into the cell nucleus where it is protected from degradation and cancer is initiated.

The researchers say that the uncovered key role of PTEN degradation provides a potential route to new therapeutic strategies. They believe that a class of drugs, the proteasome inhibitors, that selectively block the degrading effects of ubiquitination, should now be studied as possible treatments for cancers with PTEN mutations.