Publications

Huttlin EL, Bruckner RJ, Paulo JA, Cannon JR, Ting L, Baltier K, Colby G, Gebreab F, Gygi MP, Parzen H, Szpyt J, Tam S, Zarraga G, Pontano-Vaites L, Swarup S, White AE, Schweppe DK, Rad R, Erickson BK, Obar RA, Guruharsha KG, Li K, Artavanis-Tsakonas S, Gygi SP, Harper JW. Architecture of the human interactome defines protein communities and disease networks. Nature. 2017 May 17. doi:10.1038/nature22366.

Yang W, Nagasawa K, Münch C, Xu Y, Satterstrom K, Jeong S, Hayes SD, Jedrychowski MP, Vyas FS, Zaganjor E, Guarani V, Ringel AE, Gygi SP, Harper JW, Haigis MC. (2016) Mitochondrial Sirtuin Network Reveals Dynamic SIRT3-Dependent Deacetylation in Response to Membrane Depolarization. Cell online edition.  

Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA. Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. Cell. 2016 Jun 2;165(6):1440-53.
Dong R, Saheki Y, Swarup S, Lucast L, Harper JW, De Camilli P. Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P. Cell. 2016 Jul 14;166(2):408-23.
Harper JW, Bennett EJ. Proteome complexity and the forces that drive proteome imbalance. Nature. 2016 Sep 14;537(7620):328-38.
Rose CM, Isasa M, Ordureau A, Prado MA, Beausoleil SA, Jedrychowski MP, Finley DJ, Harper JW, Gygi SP. Highly Multiplexed Quantitative Mass Spectrometry Analysis of Ubiquitylomes. Cell Systems 2016 Sep 21. pii: S2405-4712(16)30264-2.
Scott DC, Rhee DY, Duda DM, Kelsall IR, Olszewski JL, Paulo JA, de Jong A, Ovaa H, Alpi AF, Harper JW, Schulman BA. Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation. Cell. 2016 Aug 25;166(5):1198-1214.
Guarani V, Jardel C, Chrétien D, Lombès A, Bénit P, Labasse C, Lacène E, Bourillon A, Imbard A, Benoist JF, Dorboz I, Gilleron M, Goetzman ES, Gaignard P, Slama A, Elmaleh-Bergès M, Romero NB, Rustin P, Ogier de Baulny H, Paulo JA, Harper JW, Schiff M. QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease. Elife. 2016 Sep 13;5. pii:e17163.

Nadarajan S, Mohideen F, Tzur YB, Ferrandiz N, Crawley O, Montoya A, Faull P, Snijders AP, Cutillas PR, Jambhekar A, Blower MD, Martinez-Perez E, Harper JW, Colaiacovo MP. (2016) The MAP kinase pathway coordinates crossover designation with disassembly of synaptonemal complex proteins during meiosis. Elife doi: 10.7554/eLife.12039. 

Bui DA, Lee W, White AE, Harper JW, Schackmann RC, Overholtzer M, Selfors LM, Brugge JS. (2016) Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Sci Signal doi:10.1126/scisignal.aaa9227. 

Zhang W, Wu KP, Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS. (2016) System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes. Molecular Cell 62:121-136. 

Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, Wyant GA, Wang T, Harper JW, Gygi SP, Sabatini DM.  (2016) The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. Cell 165:153-164.

Feng Y, Backues SK, Baba M, Heo JM, Harper JW, Klionsky DJ. (2016) Phosphorylation of Atg9 regulates movement to the phagophore assembly site and the rate of autophagosome formation. Autophagy 12:648-658. 

Raman M, Sergeev M, Garnaas M, Lydeard JR, Huttlin EL, Goessling W, Shah JV, Harper JW. (2015) Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis. Nature Cell Biology 17:1356-1369.
Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW. (2015) The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy. Molecular Cell 60:7-20.
Izhar L, Adamson B, Ciccia A, Lewis J, Pontano-Vaites L, Leng Y, Liang AC, Westbrook TF, Harper JW, Elledge SJ. (2015) A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors. Cell Reports 11:1486-1500.
Pickrell AM, Huang CH, Kennedy SR, Ordureau A, Sideris DP, Hoekstra JG, Harper JW, Youle RJ. (2015) Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons following Mitochondrial DNA Mutagenic Stress. Neuron 87:371-881.
Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, Tam S, Zarraga G, Colby G, Baltier K, Dong R, Guarani V, Vaites LP, Ordureau A, Rad R, Erickson BK, Wühr M, Chick J, Zhai B, Kolippakkam D, Mintseris J, Obar RA, Harris T, Artavanis-Tsakonas S, Sowa ME, De Camilli P, Paulo JA, Harper JW, Gygi SP. (2015) The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 162:425-440.

Guarani V, McNeill EM, Paulo JA, Huttlin EL, Fröhlich F, Gygi SP, Van Vactor D, Harper JW. (2015) QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology. Elife  doi: 10.7554/eLife.06265. 

Ordureau A, Münch C, Harper JW. (2015) Quantifying Ubiquitin Signaling. Molecular Cell 58:660-676. 

Ordureau A, Heo JM, Duda DM, Paulo JA, Olszewski JL, Yanishevski D, Rinehart J, Schulman BA*, Harper JW*. (2015) Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy. Proc Natl Acad Sci U S A. 112:6637-6642. *, co-corresponding authors 

Ordureau A, Sarraf SA, Duda DM, Heo J-M, Jedrykowski MP, Sviderskiy V, Olszewski JL, Koerber JT, Xie T, Beausoleil SA, Wells JA, Gygi SP, Schulman BA, and Harper JW (2014) Quantitative proteomics reveal a feed-forward mechanism for mitochondrial PARKIN translocation and UB chain synthesis. Molecular Cell, 56: 360–375.

Ikeuchi Y, Dadakhujaev S, Chandhoke AS, Huynh MA, Oldenborg A, Ikeuchi M, Deng L, Bennett EJ, Harper JW, Bonni A, Bonni S. (2014) TIF1γ Protein Regulates Epithelial-Mesenchymal Transition by Operating as a Small Ubiquitin-like Modifier (SUMO) E3 Ligase for the Transcriptional Regulator SnoN1. J Biol Chem. 289:25067-25078.

Vaites LL, Harper JW. (2014) Spindle assembly factor protection. Molecular Cell 53:165-166.

Ordureau A, Harper JW. (2014) Cell biology: balancing act. Nature 510:347-348. News and Views

Scott DC, Sviderskiy VO, Monda JK, Lydeard JR, Cho SE, Harper JW, Schulman BA. (2014) Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8. Cell 157:1671-1684.

Fischer ES, Böhm K, Lydeard JR, Yang H, Stadler MB, Cavadini S, Nagel J, Serluca F, Acker V, Lingaraju GM, Tichkule RB, Schebesta M, Forrester WC, Schirle M, Hassiepen U, Ottl J, Hild M, Beckwith RE, Harper JW, Jenkins JL, Thomä NH. (2014) Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512:49-53.

Mancias JD, Wang X, Gygi SP, Harper JW*, and Kimmelman AC*. (2014) Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature, 509:105-109. (image: Eric D. Smith and Joseph D. Mancias)

Guarani, V., Paulo, J., Zhai, B., Huttlin, E.L., Gygi, S.P., and Harper, J.W. (2014) TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial Complex I assembly factor through association with the MCIA complex. Molecular and Cellular Biology, 34:847-861.

Mosammaparast N, Kim H, Laurent B, Zhao Y, Lim HJ, Majid MC, Dango S, Luo Y, Hempel K, Sowa ME, Gygi SP, Steen H, Harper JW, Yankner B, Shi Y. (2013) The histone demethylase LSD1/KDM1A promotes the DNA damage response. J Cell Biol. 203:457-470.

Mejia LA, Litterman N, Ikeuchi Y, de la Torre-Ubieta L, Bennett EJ, Zhang C, Harper JW, Bonni A. (2013) A Novel Hap1-Tsc1 Interaction Regulates Neuronal mTORC1 Signaling and Morphogenesis in the Brain. J Neurosci. 33:18015-21.

Lydeard JR, Schulman BA, Harper JW. (2013) Building and remodelling Cullin-RING E3 ubiquitin ligases. EMBO Rep. Nov 15. doi: 10.1038/embor.2013.173.

Tan, M., Lim, S., Bennett, E.J., Shi, Y., and Harper, J.W. (2013) Parallel SCF Adaptor Capture Proteomics Reveals a Role for SCFFBXL17 in NRF2 Activation via BACH1 Repressor Turnover. Molecular Cell, 52, 9-24.

Chang T-K, Shravage BV, Hayes SD, Powers CM, Simin RT, Harper JW, andBaehrecke EH. (2013) Uba1 functions in Atg7- and Atg3-independent autophagy.Nature Cell Biology, 15:1067-78.

Zhang C, Mejia LA, Valnegri P, Bennett EJ, Anckar J, Jahani-Asl A, Gallardo G, Ikeuchi Y, Yamada T, Rudnicki M, Harper JW, and Bonni A. (2013) The X-linked Intellectual Disability Protein PHF6 Associates with the PAF1 Complex and Regulates Neuronal Migration in the Mammalian Brain. Neuron 78:986-993

Sarraf S, Raman M, Guarani-Pereria V, Sowa ME, Huttlin EL, Gygi SP, and Harper JW. (2013) Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496:372-376.

Martínez-Noël G, Galligan JT, Sowa ME, Arndt V, Overton TM, Harper JW, Howley PM. (2012) Identification and Proteomic Analysis of Distinct UBE3A/E6AP Protein Complexes. Mol Cell Biol 32:3095-3106.

Popovic D, Akutsu M, Novak I, Harper JW, Behrends C, Dikic I (2012) Rab GAPs in Autophagy: Regulation of endocytic and autophagy pathways by direct binding to human ATG8 modifieers. Mol Cell Biol. 32: 1733-1744.

Tan MJ, White EA, Sowa ME, Harper JW, Aster JC, Howley PM (2012) Cutaneous beta- human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling. Proc Natl Acad Sci USA, 109:E1473-80.

Christianson JC, Olzmann JA, Shaler TA, Sowa ME, Bennett EJ, Richter CM, Tyler RE, Greenblatt EJ, Harper JW and Kopito RR. (2011) Defining human ERAD networks through an integrative mapping strategy. Nature Cell Biology, 14; 93-105

Kim W, Bennett EJ, Huttlin EL, Guo A., Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW*, and Gygi SP*. (2010) Systematic and quantitative analysis of the ubiquitin modified proteome. Molecular Cell 44:325-340.

Scott DC, Monda JK, Bennett EJ, Harper JW, Schulman BA. (2011) N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex. Science, 334:674-678.

Lee PC, Sowa SE, Gygi SP, Harper JW . (2011) Alternative Ubiquitin Activation/Conjugation Cascades Interact with N-End Rule Ubiquitin Ligases to Control Degradation of RGS Proteins. Molecular Cell 43:392-405.

Tan M-K M, Lim H-J, Harper JW. (2011) SCFFBXO22 regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation. Mol. Cell. Biol., 31:3687-3699

O'Connell BC, Adamson B, Lydeard JR, Sowa ME, Ciccia A, Bredemeyer AL, Schlabach M, Gygi SP, Elledge SJ, Harper JW. (2010) A Genome-wide Camptothecin Sensitivity Screen Identifies a Mammalian MMS22L-NFKBIL2 Complex Required for Genomic Stability. Mol Cell. 40:645-657.

Bennett, E.J., Ruch, J., Gygi, SP, and Harper, JW. (2010) Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 143:951-965.

Litterman N, Ikeuchi Y, Gallardo G, O'Connell BC, Sowa ME, Gygi SP, Harper JW, Bonni A. (2011) An OBSL1-Cul7 Ubiquitin Ligase Signaling Mechanism Regulates Golgi Morphology and Dendrite Patterning. PLoS Biol. 9:e1001060.

Behrends, C, Sowa ME, Gygi SP, and Harper JW. (2010) Network organization of the human autophagy system. Nature 466, 68-77.

Svendsen JM, Harper JW. (2010) GEN1/Yen1 and the SLX4 complex: solutions to the problem of Holliday junction resolution. Genes Dev. 24:521-36.

Sarraf SA, Harper JW. (2010) Telomeric TuRF1 wars. Developmental Cell 18:167-168.

Raman M, Harper JW. (2009) Cell biology: Stairway to the proteasome. Nature 462:585-586.

Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA. (2009) Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Molecular Cell. 36:39-50.

Ciccia, A, Bredemeyer, AL, Sowa, ME, Terret, M-E, Jallepalli, PV, Harper, JW, and Elledge, SJ. (2009) The SIOD disorder protein SMARCAL1 is an RPA- interacting protein involved in replication fork restart. Genes and Development, 23:2415-2425.

Svendsen, J., Smogorzewska, A.,Sowa, M.E., O’Connell, B.O., Gygi, S.P., Elledge, S.J., and Harper, J.W. (2009) Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell, 138:63-77.

Sowa, M.E., Bennett, E.J., Gygi, S.P., and Harper, J.W. (2009) Defining the Human Deubiquitinating Enzyme Interaction Landscape. Cell, 138:389-403.

Lai Xu, Mathew E. Sowa, Jing Chen, Xue Li, Steven P. Gygi, and J. Wade Harper (2009) An FTS/Hook/p107FHIP Complex Interacts with and Promotes Endosomal Clustering by the Homotypic Vacuolar Protein Sorting (HOPS) Complex. Molecular Biology of the Cell, 19:5059-71 .

Schulman BA and Harper JW. Ubiquitin-like protein activation: the apex for diverse signaling pathways. Nature Reviews Molecular Cell Biology, 2009, 10:319-331. 

Ang XL and Harper JW. Global Protein Stability (GPS): a roadmap to cellular protein homeostasis. Nature Chemical Biology. 2009, 5:9-11 . (News and Views)

Ang et al. Regulation of postsynaptic rapgap spar by polo-like kinase 2 and the SCFbeta-TRCP ubiquitin ligase in hippocampal neurons. J Biol Chem. 2008, 283: 29424-32.

Jin et al. Differential roles for checkpoint kinases in DNA damage-dependent degradation of the Cdc25A protein phosphatase. J Biol Chem. 2008 283:19322-8.

Schlabach et al., Cancer proliferation gene discovery through functional genomics. Science. 2008 319:620-4.

Westbrook et al., SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature. 2008 452:370-4.

Bennett EJ, Harper JW. DNA damage: ubiquitin marks the spot. Nat Struct Mol Biol. 2008 15:20-2. 

Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol Cell. 2007 28:739-45.

Jin et al. Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging. Nature. 2007 447:1135-8.

Stegmeier et al.Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature. 2007 446:876-81.

Hao et al. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007 26:131-43.

Jin et al. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell. 2006 23:709-21.

Harper JW, Schulman BA. Structural complexity in ubiquitin recognition. Cell. 2006 124:1133-6.