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
- Speaker CRC 1430
- Press Releases
- Selected Publications
- ORCID ID
- Publication Metrics
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- 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
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2024 VCP International Conference : Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathyIn: Neurobiology of Disease , Vol. 207 2025, 106861DOI (Open Access)
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Light-Activatable Ubiquitin for Studying Linkage-Specific Ubiquitin Chain Formation KineticsIn: Advanced Science , Vol. 12 2025, Nr. 6, 2406570DOI (Open Access)
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Molecular Tweezers Block the Functional Pore of a Protein MachineIn: Journal of the American Chemical Society: JACS , Vol. 147 2025, Nr. 20, pp. 16836 – 16849DOI (Open Access)
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A modular DNA origami nanocompartment for engineering a cell-free, protein unfolding and degradation pathwayIn: Nature Nanotechnology , Vol. 19 2024, Nr. 10, pp. 1521 – 1531DOI (Open Access)
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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, e2408787121DOI (Open Access)
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Lysosomal damage sensing and lysophagy initiation by SPG20-ITCHIn: Molecular Cell 2024, pp. 1556 – 1569.e10DOI, Online Full Text (Open Access)
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The Endo-Lysosomal Damage ResponseIn: Annual Review of Biochemistry , Vol. 93 2024, Nr. 1, pp. 367 – 387DOI (Open Access)
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VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substratesIn: Nature Communications , Vol. 15 2024, Nr. 1, 2459DOI (Open Access)
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Structural basis of ubiquitin-independent PP1 complex disassembly by p97In: The EMBO Journal , Vol. 42 2023, Nr. 14, e113110DOI (Open Access)
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Targeting of client proteins to the VCP/p97/Cdc48 unfolding machineIn: Frontiers in Molecular Biosciences , Vol. 10 2023, 1142989DOI, Online Full Text (Open Access)
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The UBX domain in UBXD1 organizes ubiquitin binding at the C-terminus of the VCP/p97 AAA-ATPaseIn: Nature Communications , Vol. 14 2023, Nr. 1, 3258DOI, Online Full Text (Open Access)
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MAGED2 Is Required under Hypoxia for cAMP Signaling by Inhibiting MDM2-Dependent Endocytosis of G-Alpha-SIn: Cells , Vol. 11 2022, Nr. 16, 2546DOI (Open Access)
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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.e7DOI (Open Access)
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Ubiquitin-directed AAA+ ATPase p97/VCP unfolds stable proteins crosslinked to DNA for proteolysis by SPRTNIn: The Journal of Biological Chemistry (JBC) , Vol. 298 2022, Nr. 6, 101976DOI (Open Access)
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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)In: Autophagy , Vol. 17 2021, Nr. 1, pp. 1 – 382DOI (Open Access)
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Targeted substrate loop insertion by VCP/p97 during PP1 complex disassemblyIn: Nature Structural & Molecular Biology , Vol. 28 2021, Nr. 12, pp. 964 – 971
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A pH-sensitive fluorescent protein sensor to follow the pathway of calcium phosphate nanoparticles into cellsIn: Acta Biomaterialia , Vol. 111 2020, pp. 406 – 417
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Protein Phosphatase-1 Complex Disassembly by p97 is Initiated through Multivalent Recognition of Catalytic and Regulatory Subunits by the p97 SEP-domain AdaptersIn: Journal of Molecular Biology (JMB) , Vol. 432 2020, Nr. 23, pp. 6061 – 6074
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Regulation of lysosome integrity and lysophagy by the ubiquitin-conjugating enzyme UBE2QL1In: Autophagy , Vol. 16 2020, Nr. 1, pp. 179 – 180DOI (Open Access)
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Repair or Lysophagy : Dealing with Damaged LysosomesIn: Journal of Molecular Biology (JMB) , Vol. 432 2020, Nr. 1, pp. 231 – 239
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Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product FamilyIn: Chemistry - A European Journal , Vol. 26 2020, Nr. 39, pp. 8524 – 8531DOI (Open Access)
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Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPaseIn: Biomolecules , Vol. 9 2019, Nr. 12, 876DOI, Online Full Text (Open Access)
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The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damageIn: EMBO Reports 2019, pp. e48014DOI (Open Access)
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VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscleIn: Autophagy , Vol. 15 2019, Nr. 6, pp. 1082 – 1099DOI (Open Access)
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A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPasesIn: Angewandte Chemie International Edition , Vol. 57 2018, Nr. 6, pp. 1576 – 1580
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AP-SWATH reveals direct involvement of VCP/ p97 in integrated stress response signaling through facilitating CReP/PPP1R15B degradationIn: Molecular and Cellular Proteomics (MCP) , Vol. 17 2018, Nr. 7, pp. 1295 – 1307DOI (Open Access)
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Ubiquitin-Independent Disassembly by a p97 AAA-ATPase Complex Drives PP1 Holoenzyme FormationIn: Molecular Cell , Vol. 72 2018, Nr. 4, pp. 766 – 777DOI (Open Access)
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VCP/p97-Mediated Unfolding as a Principle in Protein Homeostasis and SignalingIn: Molecular Cell , Vol. 69 2018, Nr. 2, pp. 182 – 194DOI (Open Access)
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Delivery of the autofluorescent protein R-phycoerythrin by calcium phosphate nanoparticles into four different eukaryotic cell lines (HeLa, HEK293T, MG-63, MC3T3) : Highly efficient, but leading to endolysosomal proteolysis in HeLa and MC3T3 cellsIn: PLoS ONE , Vol. 12 2017, Nr. 6, pp. e0178260DOI (Open Access)
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Detection and Clearance of Damaged Lysosomes by the Endo-Lysosomal Damage Response and LysophagyIn: Current Biology , Vol. 27 2017, Nr. 24, pp. R1330 – R1341
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VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagyIn: The EMBO Journal , Vol. 36 2017, Nr. 2, pp. 135 – 150DOI (Open Access)
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Molecular tweezers target a protein-protein interface and thereby modulate complex formationIn: Chemical Communications: ChemComm , Vol. 52 2016, Nr. 98, pp. 14141 – 14144DOI (Open Access)
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VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break RepairIn: Molecular Cell , Vol. 64 2016, Nr. 1, pp. 189 – 198DOI (Open Access)
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The N-terminal region of the ubiquitin regulatory X (UBX) domain-containing protein 1 (UBXD1) modulates interdomain communication within the valosin-containing protein p97In: The Journal of Biological Chemistry (JBC) , Vol. 290 2015, Nr. 49, pp. 29414 – 29427DOI (Open Access)
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Inhibitor-3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore-bound protein phosphatase-1In: The EMBO Journal , Vol. 33 2014, Nr. 22, pp. 2704 – 2720DOI (Open Access)
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The VCP/p97 system at a glance : connecting cellular function to disease pathogenesisIn: Journal of Cell Science , Vol. 127 2014, Nr. 18, pp. 3877 – 3883
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The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradationIn: The FEBS Journal , Vol. 281 2014, Nr. Suppl. 1, pp. 82
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The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradationIn: Cell Cycle , Vol. 13 2014, Nr. 6, pp. 919 – 927DOI (Open Access)
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Coal mining meets chromatin research: Digging for mechanisms in epigenetic control of gene expression : Report from the 43rd Annual Meeting of the German Genetics Society on "Chromatin and Epigenetics" in Essen, GermanyIn: BioEssays , Vol. 35 2013, Nr. 2, pp. 141 – 144
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The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora AIn: The Journal of Cell Biology (JCB) , Vol. 201 2013, Nr. 4, pp. 559 – 575
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Ubiquitination of the n-terminal region of caveolin-1 regulates endosomal sorting by the VCP/p97 AAA-ATPaseIn: The Journal of Biological Chemistry (JBC) , Vol. 288 2013, Nr. 10, pp. 7363 – 7372
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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.DOI (Open Access)
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Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin systemIn: Nature Cell Biology , Vol. 14 2012, Nr. 2, pp. 117 – 123
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Expanding into new markets – VCP/p97 in endocytosis and autophagyIn: Journal of Structural Biology , Vol. 179 2012, Nr. 2, pp. 78 – 82
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p97 complexes as signal integration hubsIn: BMC Biology (incorporating Journal of Biology) , Vol. 10 2012, pp. 48DOI, Online Full Text (Open Access)
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Cdc48/p97-Ufd1-Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells.In: Journal of Cell Science , Vol. 124 2011, Nr. 9, pp. 1571 – 1580
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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 – 1123
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The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaksIn: Nature Cell Biology , Vol. 13 2011, Nr. 11, pp. 1376 – 1382
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A role for Cdc48/p97 and Aurora B in controlling chromatin condensation during exit from mitosisIn: Biochemistry and Cell Biology , Vol. 88 2010, Nr. 1, pp. 23 – 28
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Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradationIn: The Journal of Cell Biology (JCB) , Vol. 191 2010, Nr. 3, pp. 615 – 629
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Role(s) of Cdc48/p97 in mitosisIn: Biochemical Society Transactions , Vol. 36 2008, Nr. 1, pp. 126 – 130
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Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatinIn: Nature , Vol. 450 2007, Nr. 7173, pp. 1258
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Detailed structural insights into the p97-Npl4-Ufd1 interfaceIn: The Journal of Biological Chemistry (JBC) , Vol. 282 2007, Nr. 29, pp. 21361 – 21369
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NSF- and SNARE-mediated membrane fusion is required for nuclear envelope formation and completion of nuclear pore complex assembly in Xenopus laevis egg extractsIn: Journal of Cell Science , Vol. 120 2007, Nr. 16, pp. 2895 – 2903
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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
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Golgi reassembly after mitosis : The AAA family meets the ubiquitin familyIn: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research , Vol. 1744 2005, Nr. 2, pp. 108 – 119DOI (Open Access)
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The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanismIn: The Journal of Biological Chemistry (JBC) , Vol. 279 2004, Nr. 48, pp. 49609 – 49616
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Ubiquitin Interactions of NZF Zinc FingersIn: The EMBO Journal , Vol. 23 2004, Nr. 7, pp. 1411 – 1421
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VCIP135 acts as a deubiquitinating enzyme during p97–p47-mediated reassembly of mitotic Golgi fragmentsIn: The Journal of Cell Biology (JCB) , Vol. 164 2004, Nr. 7, pp. 973 – 978
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Function of the p97–Ufd1–Npl4 complex in retrotranslocation from the ER to the cytosol : dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chainsIn: The Journal of Cell Biology (JCB) , Vol. 162 2003, Nr. 1, pp. 71 – 84
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Structure and Ubiquitin Interactions of the Conserved Zinc Finger Domain of Npl4In: The Journal of Biological Chemistry (JBC) , Vol. 278 2003, pp. 20225 – 20234
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The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosisIn: Cell , Vol. 115 2003, Nr. 3, pp. 355 – 367
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Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1–Npl4In: The EMBO Journal , Vol. 21 2002, Nr. 21, pp. 5645 – 5652.
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Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assemblyIn: Nature Cell Biology , Vol. 3 2001, Nr. 12, pp. 1086 – 1091
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The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosolIn: Nature , Vol. 414 2001, pp. 652 – 656
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A complex of mammalian Ufd1 and Npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathwaysIn: The EMBO Journal , Vol. 19 2000, Nr. 10, pp. 2181 – 2192
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The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene.In: The Journal of Biological Chemistry (JBC) , Vol. 274 1999, Nr. 15, pp. 10154 – 10162
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The p47 co-factor regulates the ATPase activity of the membrane fusion protein, p97In: FEBS Letters , Vol. 437 1998, Nr. 3, pp. 255 – 257