Investigating the essential roles of Ubiquitin-like molecules and the Ubiquitin Proteasome System

Research Project 9.
Role of the SUMO specific ubiquitin ligase RNF4 in the DNA damage response.

Objectives

We are particularly interested in how SUMO modification alters transcription and have identified and determined the mechanism of action of a number of the gene products required for SUMO modification and for deconjugation. This work utilizes a diverse array of approaches ranging from X-ray crystallography to biochemistry and cell biology. We recognised that the RING domain containing protein Rnf4 function as a Ub E3 ligase with a unique specificity for polySUMO chains that is responsible for arsenic inducible, proteasomal degradation of the Promyelocytic Leukaemia (PML) protein. The objective of present work is to determine the signal transduction pathway, activated by arsenic, which leads to increased SUMO modification of PML. X-ray crystallography and NMR spectroscopy are being employed to determine the structure of the Ub E3 ligase Rnf4, bound to its polySUMO substrate and its cognate E2 conjugating enzyme.

Fellow

Triin Tamsalu