Characterization of the unconventional E2 enzyme Ube2j2, involved in non-lysine ubiquitination
|Target group:||Biochemistry, Molecular Biomedicine, Biology|
|Educational level:||Masters, Bachelor|
Folding and assembly of secretory and plasma membrane proteins take place in the endoplasmic reticulum (ER). Despite the presence of a wide variety of molecular chaperones and folding factors, newly synthesized proteins quite often fail to reach their native states. The accumulation of such misfolded proteins in the ER induces ER stress, a condition associated with multiple human diseases. To restore normal cellular function, a signal transduction pathway known as the Unfolded Protein Response (UPR) is triggered upon ER stress. This coordinated transcriptional and translational response seeks to reinstate cellular homeostasis, e.g. by increasing the cellular capacity to fold and/or degrade misfolded ER proteins, and – if unsuccessful – eventually will turn on apoptosis.
An important and integrated part of the UPR is ER-associated degradation (ERAD). By this process misfolded proteins in the ER are recognized by chaperones, retrotranslocated to the cytosol, polyubiquitinated and degraded by the proteasome. In this project, we investigate the function of the ubiquitin-conjugating E2 enzyme Ube2j2 in ERAD.
Our hypothesis is that Ube2j2 can ubiquitinate not only lysine residues (like it is most often the case), but also serine and threonine (which is unusual). We will seek to obtain experimental evidence for this idea using a wide range of experimental techniques in cell biology, protein biochemistry and structural biology. Thus depending on your preference, it will be possibile to work on different aspects of the project.
|Methods used:||Cell biology, protein biochemistry, molecular biology, structural biology (NMR)|
|Keywords:||ER-associated degradation, Protein misfolding, Ubiquitin proteasome system|