The contribution of phosphorylated Rac (Ser-71) and subsequent NADPH oxidase signaling to colon cancer developemnt

• Applicant: Dr. Janett Schwarz
• Subject Area: Pharmacology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 121821521

The Rho GTPases Rac1 and Rac2 are highly homologous and act as molecular switches to initiate downstream signaling. Phosphorylation of Rac1 at serine-71 is suspected to play a role in regulating effector binding and its activation. Both Rac1 and Rac2 regulate the activity of NADPH oxidases (Nox), which in turn generate Reactive Oxygen Species (ROS). Very little is known about the involved signals and the regulatory molecular machinery though. Nox proteins are found in virtually all tissues and have been implicated in such biological processes as cell proliferation, apoptosis, cell signaling, motility, and transcription. Evidence exists that Nox proteins play a key role in colon cancer formation. The studies proposed in this application focus on further investigation of - signaling pathways leading to phosphorylation of Rac1 at serine-71 (chapters A.2/D.1) - molecular mechanism by which phosphorylated Rac1/Rac2 affects Nox-dependent ROS generation (chapters A.3/D.2) - physiological relevance of phosphorylated Rac1 in mechanism of colon cancer (chapters A.4/D.3) The findings will help to understand the role of phosphorylated Rho GTPases Rac1 and Rac2 in regulating Nox proteins and their involvement in mechanisms promoting cancer formation and growth.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Céline Dermardirossian, Ph.D.