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Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL.
During the course of their development, it was discovered that the capacity of a PROTAC to induce degradation involves more than just target binding: the identity of the inhibitor warhead and the recruited E3 ligase largely determine the degradation profiles of the compounds. Expand
The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. elegans
In vivo analyses reveal the elongated canyon of the UCS domain as a myosin-binding site and show that multimeric UNC-45 chains support organization of sarcomeric repeats. Expand
The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression
TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II, and uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing. Expand
Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin
In vitro reconstitution and structural biology is used to characterize the interplay between UNC-45 and muscle myosin MHC-B in insect cells and uncover the molecular basis of temperature-sensitive UNC- 45 mutations underlying one of the most prominent motility defects in C. elegans. Expand
UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins
In vitro and in vivo experiments are performed and it is shown that UFD-2 has E3 ligase activity and that it ubiquitinates unfolded myos in muscle cells using the C. elegans myosin chaperone UNC-45 as an adaptor protein. Expand
Targeted protein unfolding uncovers a Golgi-specific transcriptional stress response
The Golgi’s ability to sense misfolded proteins and establish new aspects of Golgi autoregulation are highlighted and previously uncharacterized genes that are essential for Golgi structural integrity are revealed. Expand
Myosin chaperones☆
Graphical abstract
Protein folding state-dependent sorting at the Golgi apparatus
The existence of checkpoints at which QC substrates are selected for Golgi export and lysosomal degradation are highlighted, and the steady-state ER localization of misfolded proteins, observed for several disease-causing mutants, may have different origins. Expand
UNC-45 from C. elegans forms a chaperone chain
Der funktionelle Zusammenschluss von Motorproteinen ist die Basis fur aktive Bewegung auf zellularem aber auch auf organismischem Niveau. Um die Erzeugung von Kraft auf einer soliden Basis zuExpand