Around 75% of all breast cancers are positive for the Estrogen Receptor (ER), which is considered the main driver of the disease. In a siRNA screen targeting all 781 E1, E2 and E3 ligases throughout the human genome, we set out to discover novel regulators of ER stability. We identified TRIM33 as a crucial factor to regulate ER levels and activity. We aim to unravel the biological interplay between ER function and TRIM33, and explore how this interaction can be therapeutically exploited using novel inhibitors.

Prostate cancer is one of the leading cancer deaths for men. By applying state-of-the-art techniques in molecular biology and biochemistry, we will investigate how TRIM25 controls androgen receptor activity and proliferation and migration of prostate cancer cells and elucidate its suitability as a target for drug development.

Institution information: University Clermont-Auvergne (UCA) and INRA, Clermont-Ferrand, France. Clermont-Ferrand is a vibrant student city and UCA is committed to developing educational programs for an international public (dual-award programs) and to enhancing its research at an international level. Since its creation, UCA has embraced the two main European political roadmaps for 2014-2020 through the Erasmus+ and Horizon 2020 programs.

TRIM32 is the gene responsible for Limb Girdle Muscular Dystrophy type  2H and Sarcotubular Myopathy. The TRIM32 gene product is an E3 ubiquitin  ligase for which many substrates have been reported. To unravel its  function in muscular dystrophy, it is important to understand how TRIM32  pleiotropy is achieved. TRIM32 ability to homo-interact, thus offering  several RING moieties to E2 binding, and to interact with different E2  enzymes can underlie TRIM32 potential to form different complex  combinations.

Lafora progressive myoclonus epilepsy is caused by mutations in the TRIM-like E3-ubiquitin ligase malin. This study will identify the role of malin in pathophysiology. Interactomics and proteomic techniques will be used to identify substrates of malin. We will also pay attention to the deubiquitinases that accompany malin in its action.

TRIM17 increases α-synuclein expression by inhibiting ubiquitination/degradation of the transcription factor ZSCAN21 mediated by TRIM41.

The aim is to assess:

1. The role of this pathway in Parkinson’s disease models;
2. The impact of TRIM41 and ZSCAN21 mutations identified in patients;
3. The molecular mechanisms of TRIM41 inhibition by TRIM17.