Functional studies on the kB-Ras proteins

• Applicant: Dr. Andrea Oeckinghaus
• Subject Area: Pharmacology
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 89147004

κB-Ras1 and 2 are two evolutionary conserved Ras-like proteins. They differ from classical Ras proteins in certain amino acids, otherwise only found in the oncogenic forms of Ras, and in the absence of the typical farnesylation site. This suggests that they might function quite differently than classical Ras GTPases. Although little is known about the function of κB-Ras proteins, biochemical experiments have shown that they can interfere with activation of the transcription factor NF-κB. NF-κB activity is mainly regulated by the inhibitory proteins IκBα and IκBβ. κB-Ras proteins specifically interact with IκBβ and interfere with its stimulus-induced degradation. Thus, κB-Ras proteins might provide an explanation for the observed delayed and incomplete degradation of IκBβ, which is required for persistent NF-κB activity. Here I propose to characterize κB-Ras deficient mice to establish an understanding of the overall biological role of κB-Ras proteins in vivo. My studies aim to elucidate the molecular mechanisms of κB-Ras function in NF-κB signalling and the resulting physiological roles of these proteins in NF-κB dependent processes like the immune response or the development of hematopoetic malignancies.

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