The role of the deubiquitinating enzymes Cyld and A20 in B cell lymphomagenesis

• Applicant: Dr. Nadine Hövelmeyer
• Subject Area: Cell Biology ; African, American and Oceania Studies
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 165257285

B-lymphocytes participate in immune responses that require their proliferation, differentiation and hypermutation. Many of these processes, particularly hypermutation, may lead to oncogenic mutations. Indeed, many types of lymphomas originate from defects during hypermutation occurring in the germinal centers. Mutations in NFκB signaling molecules and in negative regulators such as CYLD and A20 have been identified in B cell lymphomas. These deubiquitinating enzymes remove activating lysine-63 linked ubiquitin chains from numerous NFκB signaling molecules, including the IκB molecule and the oncogene Bcl-3 thus controlling their activity. This project aims at investigating the role of CYLD and A20 in lymphomagenesis using mice with conditional mutations in CYLD and A20 in B cells. These mice will be exposed to conditions that favor lymphoma development, such as overexpression of the oncogenes Bcl-3 and/or Bcl-6. Our studies will contribute to the understanding of the mechanisms leading to B cell lymphoma development potentially setting the ground for novel therapeutic interventions.

• DFG Programme: Research Grants