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Research
Research Interests
Our lab is interested in the regulation of multiubiquitylation pathways
of the ubiquitin proteasome system. Besides the already known E1, E2
and E3 enzymes additional modulators of substrate ubiquitylation such
as E4 enzymes and the AAA ATPase CDC-48/p97 have been identified. The
detailed analysis of binding partners and substrates of CDC-48 and the
E4 enzymes UFD-2 and CHN-1 combined with structural data will help us
to decipher the exact mechanism of multiubiquitin chain assembly in
different physiologically relevant processes. We identified CDC-48/p97
to implicate myosin assembly and muscle maintenance in the
pathophysiology of inclusion body myopathy (IBMPFD). But how mutations
in p97 establish protein aggregates and finally inclusion bodies is not
understood at present. Therefore, our future studies will investigate
the relationship between ubiquitin-dependent degradation of misfolded
proteins, inclusion body formation and age-related diseases.
Another major aspect will be the identification of new components of
the UPS involved in tissue-specific protein degradation. Therefore, we
are establishing a neuron-specific in vivo degradation assay in C.
elegans. The isolation of new genes implicated in neuron-specific
protein degradation and their characterization will open a completely
new avenue of research. Moreover, this might give further insights into
the connection between the UPS and age-related neurodegenerative
diseases like Parkinson’s and Alzheimer’s disease.
Regulation
of myosin assembly
ER-associated
protein degradation
New
Interactors of CDC-48
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