Role of the ubiquitin-like modifier FAT10 in protein degradation and ...
Role of the ubiquitin-like modifier FAT10 in protein degradation and ...
Role of the ubiquitin-like modifier FAT10 in protein degradation and ...
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Contents<br />
Acknowledgements 3<br />
Summary / Zusammenfassung 4<br />
English . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4<br />
Deutsch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6<br />
Introduction 9<br />
Prote<strong>in</strong> Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9<br />
The Ubiquit<strong>in</strong>-Proteasome-System . . . . . . . . . . . . . . . . . . . . . . . 10<br />
The Proteasome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10<br />
The 20S Proteasome . . . . . . . . . . . . . . . . . . . . . . . . 10<br />
The 26S Proteasome . . . . . . . . . . . . . . . . . . . . . . . . 11<br />
Ubiquit<strong>in</strong> <strong>and</strong> Ubiquit<strong>in</strong>-Like Prote<strong>in</strong>s . . . . . . . . . . . . . . . . . . 14<br />
Ubiquit<strong>in</strong> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14<br />
Ubiquit<strong>in</strong>-Like Prote<strong>in</strong>s . . . . . . . . . . . . . . . . . . . . . . 18<br />
Ubiquit<strong>in</strong>-Like Modifiers . . . . . . . . . . . . . . . . . . . . . . 18<br />
<strong>FAT10</strong> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21<br />
Ubiquit<strong>in</strong> Doma<strong>in</strong> Prote<strong>in</strong>s . . . . . . . . . . . . . . . . . . . . 24<br />
NUB1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26<br />
The Autophagy-Lysosome System . . . . . . . . . . . . . . . . . . . . . . . . 28<br />
Misfolded Prote<strong>in</strong> Stress, Aggresomes <strong>and</strong> <strong>the</strong> Connection between Au-<br />
tophagy <strong>and</strong> <strong>the</strong> UPS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29<br />
HDAC6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33<br />
Chapter 1: The UBA doma<strong>in</strong>s <strong>of</strong> NUB1L are required for b<strong>in</strong>d<strong>in</strong>g but not for<br />
accelerated <strong>degradation</strong> <strong>of</strong> <strong>the</strong> <strong>ubiquit<strong>in</strong></strong>-<strong>like</strong> <strong>modifier</strong> <strong>FAT10</strong> 36<br />
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37<br />
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38<br />
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40<br />
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51<br />
Experimental Procedures . . . . . . . . . . . . . . . . . . . . . . . . . 56<br />
1