Christian Schlieker, PhD
Research & Publications
Biography
News
Research Summary
Mechanisms of membrane dynamics in relation to nuclear envelopathies and viral infection
Nuclear envelopathies are a diverse group of congenital diseases that are caused by mutations affecting proteins in the nuclear envelope or lamina. We hypothesize that envelopathy-associated alleles act at least in part through a gain of function mechanism that leads to a poisoning of nuclear membrane dynamics. Our goal is to unravel the cellular mechanisms that regulate protein homeostasis in the nuclear periphery, and to elucidate the role that these pathways play in muscular dystrophies, premature aging and related envelopathies. We exploit viral proteins known to manipulate the nuclear envelope as a novel approach to identify cellular factors involved in protein turnover and non-canonical nuclear transport via vesicular intermediates.
Specialized Terms: DYT1 Dystonia, Membrane dynamics; Torsin ATPases; Alternative nuclear transport (nuclear egress); Protein quality control; viral pathogenesis
Coauthors
Research Interests
Biochemistry; Biophysics; Cell Biology; Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Selected Publications
- Coordinating nucleoporin condensation and nuclear pore complex assemblyKuiper E, Prophet S, Schlieker C. Coordinating nucleoporin condensation and nuclear pore complex assembly. FEBS Letters 2023, 597: 2534-2545. PMID: 37620293, DOI: 10.1002/1873-3468.14725.
- Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteinsTsai P, Cameron C, Forni M, Wasko R, Naughton B, Horsley V, Gerstein M, Schlieker C. Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins. Cell Reports 2022, 41: 111675. PMID: 36417855, PMCID: PMC9827541, DOI: 10.1016/j.celrep.2022.111675.
- Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activitiesProphet SM, Rampello AJ, Niescier RF, Gentile JE, Mallik S, Koleske AJ, Schlieker C. Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities. Nature Cell Biology 2022, 24: 1630-1641. PMID: 36302970, PMCID: PMC10041656, DOI: 10.1038/s41556-022-01001-y.
- p97/UBXD1 Generate Ubiquitylated Proteins That Are Sequestered into Nuclear Envelope Herniations in Torsin-Deficient CellsProphet SM, Naughton BS, Schlieker C. p97/UBXD1 Generate Ubiquitylated Proteins That Are Sequestered into Nuclear Envelope Herniations in Torsin-Deficient Cells. International Journal Of Molecular Sciences 2022, 23: 4627. PMID: 35563018, PMCID: PMC9100061, DOI: 10.3390/ijms23094627.
- Nodal modulator (NOMO) is required to sustain endoplasmic reticulum morphologyAmaya C, Cameron C, Devarkar SC, Seager S, Gerstein MB, Xiong Y, Schlieker C. Nodal modulator (NOMO) is required to sustain endoplasmic reticulum morphology. Journal Of Biological Chemistry 2021, 297: 100937. PMID: 34224731, PMCID: PMC8327139, DOI: 10.1016/j.jbc.2021.100937.
- Lipid and protein dynamics that shape nuclear envelope identityBahmanyar S, Schlieker C. Lipid and protein dynamics that shape nuclear envelope identity. Molecular Biology Of The Cell 2020, 31: 1315-1323. PMID: 32530796, PMCID: PMC7353140, DOI: 10.1091/mbc.e18-10-0636.
- Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2Rampello AJ, Laudermilch E, Vishnoi N, Prophet SM, Shao L, Zhao C, Lusk CP, Schlieker C. Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2. Journal Of Cell Biology 2020, 219: e201910185. PMID: 32342107, PMCID: PMC7265317, DOI: 10.1083/jcb.201910185.
- The Role of Torsin AAA+ Proteins in Preserving Nuclear Envelope Integrity and Safeguarding Against DiseaseRampello AJ, Prophet SM, Schlieker C. The Role of Torsin AAA+ Proteins in Preserving Nuclear Envelope Integrity and Safeguarding Against Disease. Biomolecules 2020, 10: 468. PMID: 32204310, PMCID: PMC7175109, DOI: 10.3390/biom10030468.
- An unbiased approach de-livers unexpected insight into torsin biologyProphet SM, Schlieker C. An unbiased approach de-livers unexpected insight into torsin biology. Journal Of Clinical Investigation 2019, 129: 4576-4579. PMID: 31589164, PMCID: PMC6819095, DOI: 10.1172/jci132442.
- Methodologies to monitor protein turnover at the inner nuclear membraneTsai PL, Zhao C, Schlieker C. Methodologies to monitor protein turnover at the inner nuclear membrane. 2019, 619: 47-69. PMID: 30910029, PMCID: PMC6457266, DOI: 10.1016/bs.mie.2018.12.033.
- Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1: a novel mode of regulation for AAA+ ATPasesChase A, Laudermilch E, Wang J, Shigematsu H, Yokoyama T, Schlieker C. Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1: a novel mode of regulation for AAA+ ATPases. The FASEB Journal 2018, 32: 114.1-114.1. DOI: 10.1096/fasebj.2018.32.1_supplement.114.1.
- Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1Chase AR, Laudermilch E, Wang J, Shigematsu H, Yokoyama T, Schlieker C. Dynamic functional assembly of the Torsin AAA+ ATPase and its modulation by LAP1. Molecular Biology Of The Cell 2017, 28: 2765-2772. PMID: 28814508, PMCID: PMC5638581, DOI: 10.1091/mbc.e17-05-0281.
- Dissecting Torsin/cofactor function at the nuclear envelope: a genetic studyLaudermilch E, Tsai PL, Graham M, Turner E, Zhao C, Schlieker C. Dissecting Torsin/cofactor function at the nuclear envelope: a genetic study. Molecular Biology Of The Cell 2016, 27: 3964-3971. PMID: 27798237, PMCID: PMC5156537, DOI: 10.1091/mbc.e16-07-0511.
- The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutationsTsai PL, Zhao C, Turner E, Schlieker C. The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. ELife 2016, 5: e16011. PMID: 27336722, PMCID: PMC4951196, DOI: 10.7554/elife.16011.
- Site-specific Proteolysis Mobilizes TorsinA from the Membrane of the Endoplasmic Reticulum (ER) in Response to ER Stress and B Cell Stimulation*Zhao C, Brown RS, Tang CH, Hu CC, Schlieker C. Site-specific Proteolysis Mobilizes TorsinA from the Membrane of the Endoplasmic Reticulum (ER) in Response to ER Stress and B Cell Stimulation*. Journal Of Biological Chemistry 2016, 291: 9469-9481. PMID: 26953341, PMCID: PMC4850287, DOI: 10.1074/jbc.m115.709337.
- A designed repeat protein as an affinity capture reagent.Speltz EB, Brown RS, Hajare HS, Schlieker C, Regan L. A designed repeat protein as an affinity capture reagent. Biochemical Society Transactions 2015, 43: 874-80. PMID: 26517897, PMCID: PMC5683849, DOI: 10.1042/bst20150091.
- The Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1Turner EM, Brown RS, Laudermilch E, Tsai PL, Schlieker C. The Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1. Journal Of Virology 2015, 89: 8444-8452. PMID: 26041288, PMCID: PMC4524217, DOI: 10.1128/jvi.01143-15.
- The mechanism of Torsin ATPase activationBrown RS, Zhao C, Chase AR, Wang J, Schlieker C. The mechanism of Torsin ATPase activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e4822-e4831. PMID: 25352667, PMCID: PMC4234599, DOI: 10.1073/pnas.1415271111.
- Arresting a Torsin ATPase Reshapes the Endoplasmic Reticulum*Rose AE, Zhao C, Turner EM, Steyer AM, Schlieker C. Arresting a Torsin ATPase Reshapes the Endoplasmic Reticulum*. Journal Of Biological Chemistry 2013, 289: 552-564. PMID: 24275647, PMCID: PMC3879577, DOI: 10.1074/jbc.m113.515791.
- Regulation of Torsin ATPases by LAP1 and LULL1Zhao C, Brown RS, Chase AR, Eisele MR, Schlieker C. Regulation of Torsin ATPases by LAP1 and LULL1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e1545-e1554. PMID: 23569223, PMCID: PMC3637692, DOI: 10.1073/pnas.1300676110.
- A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentationSehrawat S, Koenig PA, Kirak O, Schlieker C, Fankhauser M, Ploegh HL. A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation. Blood 2012, 121: 1145-1156. PMID: 23243279, PMCID: PMC3575758, DOI: 10.1182/blood-2012-08-447409.
- Enzymatic Blockade of the Ubiquitin-Proteasome PathwayErnst R, Claessen JH, Mueller B, Sanyal S, Spooner E, van der Veen AG, Kirak O, Schlieker CD, Weihofen WA, Ploegh HL. Enzymatic Blockade of the Ubiquitin-Proteasome Pathway. PLOS Biology 2011, 8: e1000605. PMID: 21468303, PMCID: PMC3066133, DOI: 10.1371/journal.pbio.1000605.
- Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifierVan der Veen AG, Schorpp K, Schlieker C, Buti L, Damon JR, Spooner E, Ploegh HL, Jentsch S. Role of the ubiquitin-like protein Urm1 as a noncanonical lysine-directed protein modifier. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 1763-1770. PMID: 21209336, PMCID: PMC3033243, DOI: 10.1073/pnas.1014402108.
- The Otubain YOD1 Is a Deubiquitinating Enzyme that Associates with p97 to Facilitate Protein Dislocation from the ERErnst R, Mueller B, Ploegh HL, Schlieker C. The Otubain YOD1 Is a Deubiquitinating Enzyme that Associates with p97 to Facilitate Protein Dislocation from the ER. Molecular Cell 2009, 36: 28-38. PMID: 19818707, PMCID: PMC2774717, DOI: 10.1016/j.molcel.2009.09.016.
- A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathwaySchlieker CD, Van der Veen AG, Damon JR, Spooner E, Ploegh HL. A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 18255-18260. PMID: 19017811, PMCID: PMC2584574, DOI: 10.1073/pnas.0808756105.
- A Functional Ubiquitin-Specific Protease Embedded in the Large Tegument Protein (ORF64) of Murine Gammaherpesvirus 68 Is Active during the Course of Infection▿Gredmark S, Schlieker C, Quesada V, Spooner E, Ploegh HL. A Functional Ubiquitin-Specific Protease Embedded in the Large Tegument Protein (ORF64) of Murine Gammaherpesvirus 68 Is Active during the Course of Infection▿. Journal Of Virology 2007, 81: 10300-10309. PMID: 17634221, PMCID: PMC2045495, DOI: 10.1128/jvi.01149-07.
- Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating EnzymesSchlieker C, Weihofen WA, Frijns E, Kattenhorn LM, Gaudet R, Ploegh HL. Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating Enzymes. Molecular Cell 2007, 25: 677-687. PMID: 17349955, PMCID: PMC7110467, DOI: 10.1016/j.molcel.2007.01.033.
- A Deubiquitinating Activity Is Conserved in the Large Tegument Protein of the HerpesviridaeSchlieker C, Korbel GA, Kattenhorn LM, Ploegh HL. A Deubiquitinating Activity Is Conserved in the Large Tegument Protein of the Herpesviridae. Journal Of Virology 2005, 79: 15582-15585. PMID: 16306630, PMCID: PMC1316044, DOI: 10.1128/jvi.79.24.15582-15585.2005.
- ClpV, a unique Hsp100/Clp member of pathogenic proteobacteria.Schlieker C, Zentgraf H, Dersch P, Mogk A. ClpV, a unique Hsp100/Clp member of pathogenic proteobacteria. Biological Chemistry 2005, 386: 1115-27. PMID: 16307477, DOI: 10.1515/BC.2005.128.
- Solubilization of aggregated proteins by ClpB/DnaK relies on the continuous extraction of unfolded polypeptides.Schlieker C, Tews I, Bukau B, Mogk A. Solubilization of aggregated proteins by ClpB/DnaK relies on the continuous extraction of unfolded polypeptides. FEBS Letters 2004, 578: 351-6. PMID: 15589844, DOI: 10.1016/j.febslet.2004.11.051.
- Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB.Weibezahn J, Tessarz P, Schlieker C, Zahn R, Maglica Z, Lee S, Zentgraf H, Weber-Ban EU, Dougan DA, Tsai FT, Mogk A, Bukau B. Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB. Cell 2004, 119: 653-65. PMID: 15550247, DOI: 10.1016/j.cell.2004.11.027.
- Substrate recognition by the AAA+ chaperone ClpB.Schlieker C, Weibezahn J, Patzelt H, Tessarz P, Strub C, Zeth K, Erbse A, Schneider-Mergener J, Chin JW, Schultz PG, Bukau B, Mogk A. Substrate recognition by the AAA+ chaperone ClpB. Nature Structural & Molecular Biology 2004, 11: 607-15. PMID: 15208691, DOI: 10.1038/nsmb787.
- Poly-L-lysine enhances the protein disaggregation activity of ClpB.Strub C, Schlieker C, Bukau B, Mogk A. Poly-L-lysine enhances the protein disaggregation activity of ClpB. FEBS Letters 2003, 553: 125-30. PMID: 14550559, DOI: 10.1016/s0014-5793(03)00985-2.
- Characterization of a trap mutant of the AAA+ chaperone ClpB.Weibezahn J, Schlieker C, Bukau B, Mogk A. Characterization of a trap mutant of the AAA+ chaperone ClpB. The Journal Of Biological Chemistry 2003, 278: 32608-17. PMID: 12805357, DOI: 10.1074/jbc.M303653200.
- Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK.Mogk A, Schlieker C, Friedrich KL, Schönfeld HJ, Vierling E, Bukau B. Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK. The Journal Of Biological Chemistry 2003, 278: 31033-42. PMID: 12788951, DOI: 10.1074/jbc.M303587200.
- Roles of individual domains and conserved motifs of the AAA+ chaperone ClpB in oligomerization, ATP hydrolysis, and chaperone activity.Mogk A, Schlieker C, Strub C, Rist W, Weibezahn J, Bukau B. Roles of individual domains and conserved motifs of the AAA+ chaperone ClpB in oligomerization, ATP hydrolysis, and chaperone activity. The Journal Of Biological Chemistry 2003, 278: 17615-24. PMID: 12624113, DOI: 10.1074/jbc.M209686200.
- Angiostatin formation involves disulfide bond reduction and proteolysis in kringle 5 of plasmin.Stathakis P, Lay AJ, Fitzgerald M, Schlieker C, Matthias LJ, Hogg PJ. Angiostatin formation involves disulfide bond reduction and proteolysis in kringle 5 of plasmin. The Journal Of Biological Chemistry 1999, 274: 8910-6. PMID: 10085135, DOI: 10.1074/jbc.274.13.8910.