The deubiquitinating enzyme USP13 as a specific therapeutic target in glioblastoma

  • Gutierrez Gonzalez, Gustavo, (Administrative Promotor)

Project Details

Description

Glioblastoma is the most common and aggressive brain tumor in humans.
Currently, most patients die in the months following their diagnoses.
Chemotherapeutic agents for this cancer are scarce and non-specific.
Temozolomide is almost systematically used to treat glioblastoma. Its mechanism of action is based on its ability to alkylate/methylate DNA, damaging it, and killing the tumor along with normal cells.

Therefore, new drugs and treatments are urgently needed to fight glioblastoma. Molecular understanding of the signaling pathways altered in this deleterious cancer is crucial to foster the design of more specific agents against this disease. The ubiquitin ligase Skp2 has emerged as an important oncogene involved in the etiology of glioblastoma, through the control of the cell proliferation inhibitor p27.

We have recently identified a protein called USP13, as an important positive regulator of the oncogenic action of Skp2 in cells. In this application, we propose to study the role and regulation of the
USP13-Skp2-p27 axis in glioblastoma. We hypothesize that in glioblastoma, abnormally elevated levels of USP13 are responsible for the elevated levels (and activity) of Skp2, which in turn instigates p27 degradation and unrestrained cell proliferation.

Overall, we aim to establish the role of USP13 in the etiology of glioblastoma but more importantly we will test the hypothesis that inhibition of USP13 could serve as a tailored therapeutic agent for glioblastoma.
AcronymFWOAL711
StatusFinished
Effective start/end date1/01/1431/12/16

Flemish discipline codes

  • Cancer therapy
  • Medical biotechnology

Keywords

  • Biology