Regulation des Abbaus von Cdc48-Substraten durch die antagonistischen Aktivitäten von Ufd2 und Ufd3

Rumpf, Sebastian (2006): Regulation des Abbaus von Cdc48-Substraten durch die antagonistischen Aktivitäten von Ufd2 und Ufd3. Dissertation, LMU München: Fakultät für Biologie

Abstract

The ubiquitin-proteasome system (UPS) is the major system for nucleo-/cytoplasmic proteolysis in eukaryotes. Here, proteolytic substrates are recognized by the proteasome, a large protease, after their covalent modification with chains of the small protein ubiquitin. Chaperones are important components of the UPS. In yeast, the AAA ATPase Cdc48 mediates the degradation of artificial Ubiquitin Fusion Degradation (UFD) substrates and of Spt23 p90, a transcription factor that regulates the OLE1 gene. In these processes, Cdc48 is assisted by multiple accessory factors, such as the ubiquitin E4 enzyme Ufd2 or Ufd3, a protein of unclear function. ufd3 mutants display certain similarities to mutants in deubiquitylating enzymes. Here, I show that Ufd2/E4 and Ufd3 bind to Cdc48 via the same interaction site and compete with each other for Cdc48 binding. Ufd2 binding results in substrate multiubiquitylation and degradation via the proteasomal receptors Rad23 and Dsk2, which interact with Ufd2. Ufd3 binding to Cdc48 blocks this pathway and results in the stabilization of Cdc48 substrates. In this function, Ufd3 is assisted by the newly identified deubiquitylating enzyme Otu1 which also interacts with Cdc48. In conclusion, the stability of Cdc48 substrates is determined by an equilibrium between the antagonistic activities of Ufd2/E4, Ufd3 and Otu1.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Cdc48, ubiquitin, E4, Ufd3, Rad23
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 14. Juni 2006
• 1. Bericht­erstatter:in: Jentsch, Stefan