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Projekt
Die Rolle des COP9 Signalosoms bei der Regulation der Ubiquitin- und Proteasom-abhängigen Proteolyse von p53, c-Jun und p27 (The role of the COP9 signalosome in the regulation of the ubiquitin- and proteasome-dependent proteolysis of p53,c-Jun and p27)
Antragsteller
Professor Dr. Wolfgang Dubiel
Fachliche Zuordnung
Biochemie
Förderung
Förderung von 1998 bis 2004
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5109336
The tumor suppressor protein p53 and c-Jun are transcription factors involved in a number of important cellular functions such as DNA repair, apoptosis and proliferation. The regulation of the stability of these proteins is essential for their intracellular functions. Both p53 and c-Jun are degraded by the 26S proteasome in an ubiquitin-dependent manner. c-Jun is known to be stabilized upon phosphorylation on Ser63 and 73. Recently we purified a protein complex, COP9 signalosome, from human red blood cells which is a homolog of the 26S proteasome lid complex and specifically phosphorylates p53 and c-Jun. We identified the specific phosphorylation sites and found that c-Jun is modified on Ser63 and 73 by COP9 signalosome in vitro. In the forthcoming application period we will focus on the physiological relevance of c-Jun and p53 phosphorylation by COP9 signalosome. We will study the impact of phosphorylation on stability and activity of the transcription factors in cells. We will continue to characterize COP9 signalosome and 26S proteasome lid to test the hypothesis that the lid is essential for degradation of transcription factors whereas its homolog, COP9 signalosome, stabilizes these proteins.
DFG-Verfahren
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