The Role of kB-Ras Proteins in the Regulation of Immune Signaling

• Applicant: Dr. Thomas Postler
• Subject Area: Immunology
• Term: from 2014 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264167063

Members of the NF-kB family of transcription factors are intricately involved in the regulation of a diverse range of biological processes, including cellular proliferation, differentiation and survival, as well as innate and adaptive immunity. This broad functionality is enabled by a complex network of regulators controlling activation of the appropriate NF-kB proteins at the appropriate time in response to specific stimuli. Understanding the nuances of this regulatory network is an essential prerequisite for therapeutic modulation of the NF-kB pathway in instances of pathological dysregulation, such as excessive or chronic inflammation. The kB-Ras proteins, kB-Ras 1 and 2, are poorly understood regulators of the NF-kB pathway. They were originally identified as interaction partners of inhibitor of kB (IkB) proteins, acting as stabilizers of IkBb and thus inhibiting NF-kB activation. The molecular mechanism underlying this regulation, however, has remained elusive. Importantly, no information is available about the physiological relevance of kB-Ras proteins for the normal function of the immune system. Preliminary data show that mice lacking the gene for kB-Ras 2 die significantly earlier from LPS-induced toxic shock syndrome than wild-type mice. This proposal aims to elucidate the mechanism by which kB-Ras proteins regulate the NF-kB pathway on a molecular level and to assess the importance of kB-Ras during acute and chronic inflammation on the basis of already established mouse models.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Sankar Ghosh