Understanding how the stability of the PTEN tumor suppressor is regulated

Ubiquitin is a small regulatory protein, which is used to control the function of other proteins when it is directly attached to them. The addition of ubiquitin, termed ubiquitination, can affect proteins in multiple ways: it can signal for their degradation, alter their cellular location, affect their activity, and promote or prevent interactions with other proteins. The lipid and protein tyrosine phosphatase, PTEN is one of the most frequently mutated tumor suppressors in human cancer and it has been reported to regulate a variety of cellular functions, such as cell proliferation, division, survival, apoptosis, and cell migration. It has been known for some years that PTEN can be ubiquitinated and that this appears to target PTEN for destruction. However, it is known that there are several different sites on PTEN at which ubiquitin can be added and the detailed mechanisms by which this regulates PTEN are still not clear. My project aims to understand the molecular details of how PTEN is regulated by ubiquitination. In the talk, I will discuss some data which shows how ubiquitination at various lysine residues on PTEN could regulate its stability and show that a ubiquitination site that has not been studied before has a strong effect on PTEN stability. Since even small changes in PTEN abundance can have significant effects on tumour formation, this may have a significant effect on PTEN’s functions to block cancer.