Protein degradation in development and aging

Protein ubiquitylation turned out to be a key posttranslational control mechanism providing different fates of targeted substrates in diverse cellular processes such as protein quality control, cell-cycle progression, signal transduction and development. Therefore, it is not surprising that recent studies have identified a role for ubiquitin in the regulation of aging, however, mechanistic aspects are completely unclear.
The main interest of the laboratory is based on age-related processes in multicellular organisms that are governed by ubiquitylation. Besides the already known ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes and ubiquitin protein E3 ligases that are required for ubiquitin-conjugation of certain protein substrates, we are interested in characterizing/identifying additional modulators involved in substrate recruitment and ubiquitin-chain assembly. Current research addresses proteostasis mechanisms focused on genome stability, protein aggregation diseases and lifespan regulation.



Selected Publications

Original Papers

The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to human myopathy.
Janiesch P.C., Kim J., Mouysset J., Barikbin R., Lochmüller H., Cassata G., Krause S., and Hoppe T. (2007).
Nat Cell Biol. 4, 379-90.

The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis.
Kuhlbrodt K., Janiesch P.C., Kevei E., Segref A., Barikbin R., and Hoppe T. (2011).
Nat Cell Biol. 13, 273-81.

CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.
Franz A., Orth M., Pirson P.A., Sonneville R., Blow J.J., Gartner A., Stemmann O., Hoppe T. (2011).
Mol Cell. 44, 85-96.

The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks.
Acs K., Luijsterburg M.S., Ackermann L., Salomons F.A., Hoppe T., Dantuma N.P. (2011).
Nat Struct Mol Biol. 18, 1345-50.

Reviews

Multiubiquitylation by E4 enzymes: one size doesn't fit all.
Hoppe T. (2005).
Trends Biochem. Sci. 30, 183-187.

Protein quality control gets muscle into shape.
Kim J., Löwe T., and Hoppe T. (2008).
Trends Cell Biol. 18, 264-72.

Life and destruction: ubiquitin-mediated proteolysis in aging and longevity.
Hoppe T. (2010).
F1000 Biol Rep. 11, 2:79.

Architecture of the CHN-1 U Box E3 Ligase Homodimer (modelled according to Zhang et al., Mol Cell., 2005).

Embryos depleted for CDC-48^UFD-1/NPL-4 stained with DAPI (DNA in blue) and anti-RAD-51 antibody (red).

C. elegans body-wall muscle cells (actin in red) with protein aggregates/inclusion bodies (green). Cell nuclei are stained with DAPI (blue).