The ubiquitin-proteasome system and transcriptional control

Protein ubiquitylation is a post-translational modification that has many outcomes. It can for example target the modified protein for degradation by the proteasome, modify protein-protein interaction network or alter the target protein activity. As such, ubiquitylation is central to cellular homeostasis. The last step of the ubiquitylation reaction is controlled by E3 ubiquitin ligases. The main family of E3 ubiquitin ligases groups the Cullin E3 RING ubiquitin ligases (CRLs). As an important protagonist of the ubiquitin-proteasome pathway, CRLs are controlled by different mechanisms. One of them involves the multiprotein complex Cop9 signalosome (CSN). The CSN is a metallo-dependent isopeptidase, which activity is essential to the correct functioning of CRLs. The catalytic subunit of the CSN, CSN5, is regulated at different levels that we have recently explored (1,2,3). Two key observations related to CSN5 have been reported: (i) its ability to exist outside of the CSN complex and (ii) its direct interaction with many important cellular protagonists, such as Hif-1α, c-Jun or E2F1. It has been suggested that CSN5, also known as Jun-activating binding protein 1 (Jab1), acts as a transcriptional co-activator. The project aims to understand the functional and structural relationship of CSN5 with these transcription factors. This is an exciting opportunity to explore the relationship between the ubiquitin-proteasome system and transcriptional control.
This project will involve preparative and analytical biochemistry, structural biology and molecular biology. Appropriate training and guidance will be provided. It is housed in the Department of Biochemistry in the Henri Wellcome Building, providing state-of-the art facilities to carry out this work. The project is strongly based on our previous work on CSN5 and on CSN (1,2,3). The group is part of an extensive network of collaborations through two European research networks (ITN UPStream http://www.upstreamproject.eu/ ; COST Proteostasis http://www.cost-proteostasis.eu/ ).

The successful applicant will be motivated, curious and dedicated to high research standards and will have a real enthusiasm for protein biochemistry and cellular signalling. Academic achievements, a CV and a statement letter will be asked in the application.

Applications are welcome from candidates who hold or expect to hold a first or upper second class degree in Biochemistry, Biophysics, Molecular Biology and related. Further information is available at http://www2.le.ac.uk/departments/biochemistry.

This project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www2.le.ac.uk/departments/gradschool/office/registration/self-funding. Informal enquiries can be made to Aude Echalier ([Email Address Removed]).



We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.