The Karolinska Institutet (KI) is a public non-profit University that is committed to improve human health through research training and information. Research at KI encompasses all aspects of medical science, from basic biomedical research to clinical research and public health. Clinical research includes nursing and dentistry and is mainly performed within the Karolinska University Hospital and other healthcare facilities in the Stockholm County. The teaching and research of KI aims to the development of new knowledge and technologies that can be directly implemented in patient care. This is achieved in close collaboration with the healthcare services and the biomedical industry.

Modulation of the ubiquitin-proteasome system (UPS) is a recurrent theme in viral oncogenesis. Current evidence indicates that specificity of the UPS is determined by: 1. the recognition of substrates by ubiquitin conjugating enzymes (E3); 2. the recognition of polyubiquitinated substrates by deubiquitinating enzymes (DUBs) that disassemble the polyubiquitin trees. Deubiquitination regulates both the efficiency and specificity of proteolysis with major consequences on a variety of cellular processes. Under INCA we want to investigate: The expression of DUBs in cells infected with oncogenic viruses and their malignant counterparts Identify putative viral DUBs and viral proteins that regulate the expression/activity of cellular DUBs Using a molecular approach based on overexpression/functional inactivation by RNA interference assess the role of viral/virus regulated DUBs in the control of cell growth and malignant transformation Using reporter screens based on functional inactivation identify DUBs that are involved in the regulation of viral gene expression and/or participate in the regulation of signal transduction pathways (e.g. TNF/CD40, Wnt/b-catenin) that are affected by viral transformation These topics will be pursued in the context of infections by Epstein-Barr virus and other oncogenic viruses and bacteria, in close collaboration with members of the INCA consortium.

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