Cells respond to stress at the core
Within the nucleus there are certain sub-compartments that change in form and location during physiological processes. Since many human diseases are associated with changes in nuclear architecture, research is hard pressed to better understand the changes occurring at the molecular level and their effects on gene expression. This will facilitate the development of new diagnosis and screening procedures as well as more novel treatments. The 'Investigation into the transduction of stress signals to the nucleus' (ITSSN) project aimed to better understand the changes taking place within the cell nucleus and structures such as nucleoli. The study wanted to help characterise what occurs during normal growth conditions as well as in response to stress. One change known to play a role in stress responses is the attachment of certain protein molecules to other protein molecules termed 'SUMOs' (small ubiquitin-like modifiers). Using the latest proteomic technology based on stable isotope labelling by/with amino acids in cell culture (SILAC) and mass spectrometry, ITSSN researchers screen for proteins in nucleoli that can be altered by SUMOs. Proteomics is the wide-ranging study of structure and functions of proteins, while SILAC is a powerful labelling method used to study cell signalling, post-transcript changes, protein-protein interaction and regulation of gene expression. The project managed to identify the proteins Nop58, dyskerin, Nhp2 and Nopp140 as major candidates for SUMO modification in the nucleolus.