A role for the ubiquitin domain protein HERP in ER-associated protein degradation [Elektronische Ressource] / von Andrea Schulze

A Role for the Ubiquitin Domain Protein HERP in ER-associated Protein Degradation Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) im Fach Biologie eingereicht an der Mathematisch-Naturwissenschaftlichen Fakultät I der Humboldt-Universität zu Berlin von Diplom-Biologin Andrea Schulze geboren am 10.03.1976 in Brilon Präsident der Humboldt-Universität zu Berlin Prof. Dr. Christoph Markschies Dekan der Mathematisch-Naturwissenschaftlichen Fakultät I Prof. Thomas Buckhout, PhD Gutachter: 1.: Prof. Dr. Peter-Michael Kloetzel 2.: Prof. Dr. Wolfgang Dubiel 3.: Prof. Rasmus Hartmann-Petersen, PhD Tag der mündlichen Prüfung: 27. September 2006 The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact. Thomas Henry Huxley ABSTRACT 3 ABSTRACT ER-associated protein degradation (ERAD) is part of the ER quality control system dealing with the accumulation of misfolded proteins in the ER. This process requires polyubiquitylation of ERAD substrates involving E3 ligases, such as HRD1, and their subsequent extraction from the ER membrane by the p97-Ufd1-Npl4 complex. Retrotranslocation of substrates into the cytosol for degradation by the 26S proteasome also involves the membrane proteins Derlin-1 and VIMP, which are associated with p97 to form a protein complex.