USP15

A gene on chromosome 12q14 that encodes an enzyme which deubiquitinates Lys-48-linked polyubiquitinated proteins, targeting them against proteasomal degradation. USP15 protects APC and HPV type-16 protein E6 against degradation via the ubiquitin proteasome pathway. It is expressed in skeletal muscle, kidneys, heart, placenta, liver, thymus, lungs and ovaries.

References in periodicals archive ?

Joan Seoane , Director of Translational Research at the Vall d'Hebron Institute of Oncology (VHIO) and ICREA Research Professor identified USP15 as a critical protein in cancer which, thanks to its molecular characteristics, shows enormous therapeutic promise.

USP15 promotes tumor progression by activating the TGFa pathway.

Seoane's team has unmasked the USP15 enzyme as activator of the TGFa chain reaction.

USP15 acts by controlling and correcting the TGFa activity in the same way that a thermostat regulates temperature.

This process is finely regulated by deubiquitinating enzymes (DUBs) such as USP15, which determine the correct level of a protein under certain physiological conditions.

In this orchestrated manner, USP15 controls and adapts the TGFa receptor stability and, therefore, the activity of the pathway.

The problem arises when, in some tumors, the USP15 gene is amplified due to genetic mutations and the enzyme is over produced.

Remarkably, this is not only a phenomenum of glioblastomas since the USP15 gene has also been found activated in other types of cancer such as breast or ovarian cancer.

Joan Seoane explained "When we inhibited USP15 in a real model of human glioblastoma, TGFa activity decreased and the tumor did not develop.