ZMB Member Hemmo Meyer
ZMB Member
Hemmo Meyer
Next ZMB-Member
Prof. Dr. Hemmo Meyer
Group
Molecular Biology ICenter of Medical Biotechnology (ZMB)
Faculty of Biology
University of Duisburg-Essen
Universitätsstr. 2
45141 Essen
- +49 201 183 4217
- Website
- Selected Publications
- ORCID ID
- Publication Metrics
- ZMB Research Program
Molecular and Chemical Cell Biology
Research Overview
Cellular homeostasis, proliferation and stress responses
Cells need to cope with a multitude of stress conditions that relentlessly inflict damage to its most vital components. This includes insults to the DNA that threatens genome stability, damage of proteins that can then form toxic aggregates, or injury of whole organelles such as mitochondria and lysosomes that releases harmful components. Cells have developed sophisticated molecular responses to these stresses that maintain protein homeostasis and organelle function, and ensure genomic stability. We are interested in deciphering these responses and uncover how they counteract stress-induced cell death and aging-related degeneration, or maintain cell proliferation.
The ubiquitin-proteasome system (UPS) is critically involved in cellular stress responses. Ubiquitination triggers degradation of damaged proteins by the proteasome, or removal of protein aggregates or hole organelles in the lysosome through autophagy. In addition, it regulates signalling pathways such as the DNA damage response and coordinates them with cell cycle progression.
A focus of our research has been the AAA+-type ATPase VCP/p97, which has emerged as a pivotal element of the UPS. It governs a variety of processes such as ER-associated degradation, ribosomal quality control, DNA damage responses as well as autophagy. Mutations in VCP/p97 in humans cause degenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), while pharmacological inhibition of VCP/p97 is considered as a strategy in cancer therapy. We have been working to reveal the molecular function of VCP/p97 and to understand how it cooperates with a host of accessory factors to trigger diverse stress responses in different compartments.
Keywords:
Cellular stress responses, proteostasis, ubiquitin-proteasome system, autophagy, lysosomal membrane permeabilization, lysophagy, mitophagy, DNA damage response, double strand break repair, cell cycle regulation.
Distribution of published plasmids through addgene.org.
Selected Publications
-
Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatasesIn: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 121 (2024) Nr. 36, e2408787121Online Full Text: dx.doi.org/ (Open Access)
-
Lysosomal damage sensing and lysophagy initiation by SPG20-ITCHIn: Molecular Cell (2024) pp. 1556 - 1569.e10Online Full Text: dx.doi.org/ (Open Access)
-
Ubiquitin profiling of lysophagy identifies actin stabilizer CNN2 as a target of VCP/p97 and uncovers a link to HSPB1In: Molecular Cell Vol. 82 (2022) Nr. 14, pp. 2633 - 2649.e7Online Full Text: dx.doi.org/ (Open Access)
-
Ubiquitin-Independent Disassembly by a p97 AAA-ATPase Complex Drives PP1 Holoenzyme FormationIn: Molecular Cell Vol. 72 (2018) Nr. 4, pp. 766 - 777Online Full Text: dx.doi.org/ (Open Access)
-
VCP/p97-Mediated Unfolding as a Principle in Protein Homeostasis and SignalingIn: Molecular Cell Vol. 69 (2018) Nr. 2, pp. 182 - 194Online Full Text: dx.doi.org/ (Open Access)
-
Detection and Clearance of Damaged Lysosomes by the Endo-Lysosomal Damage Response and LysophagyIn: Current Biology Vol. 27 (2017) Nr. 24, pp. R1330 - R1341Online Full Text: dx.doi.org/
-
VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break RepairIn: Molecular Cell Vol. 64 (2016) Nr. 1, pp. 189 - 198Online Full Text: dx.doi.org/ (Open Access)
-
Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopyIn: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 109 (2012) pp. 1098 - 1103.Online Full Text: dx.doi.org/ (Open Access)
-
Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin systemIn: Nature Cell Biology Vol. 14 (2012) Nr. 2, pp. 117 - 123Online Full Text: dx.doi.org/
-
Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutationsIn: Nature Cell Biology Vol. 13 (2011) Nr. 9, pp. 1116 - 1123Online Full Text: dx.doi.org/
-
The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaksIn: Nature Cell Biology Vol. 13 (2011) Nr. 11, pp. 1376 - 1382Online Full Text: dx.doi.org/
-
Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatinIn: Nature Vol. 450 (2007) Nr. 7173, pp. 1258
-
Structural insights into the p97-Ufd1-NpI4 complexIn: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 104 (2007) Nr. 2, pp. 467 - 472
-
Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assemblyIn: Nature Cell Biology Vol. 3 (2001) Nr. 12, pp. 1086 - 1091
-
The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosolIn: Nature Vol. 414 (2001) pp. 652 - 656
-
Structure of the AAA ATPase p97In: Molecular Cell Vol. 6 (2000) Nr. 6, pp. 1473 - 1484Online Full Text: dx.doi.org/