Recognition of nonproline N-terminal residues by the Pro/N-degron pathway

Dong, Cheng; Chen, Shun-Jia; Melnykov, Artem; Weirich, Sara; Sun, Kelly; Jeltsch, Albert; Varshavsky, Alexander; Min, Jinrong

doi:10.1073/pnas.2007085117

Title: Recognition of nonproline N-terminal residues by the Pro/N-degron pathway

Journal Article · 07 June 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.2007085117 · OSTI ID:1642239

^[1];

^[2]; Melnykov, Artem ^[3]; Weirich, Sara ^[4]; Sun, Kelly ^[5]; Jeltsch, Albert ^[4]; Varshavsky, Alexander ^[2]; Min, Jinrong ^[6]

Tianjin Medical Univ. (China)
California Inst. of Technology (CalTech), Pasadena, CA (United States)
Auragent Bioscience, St. Louis, MO (United States)
Univ. Stuttgart (Germany)
Univ. of Toronto, ON (Canada)
Univ. of Toronto, ON (Canada); Central China Normal Univ., Wuhan (China)

Eukaryotic N-degron pathways are proteolytic systems whose unifying feature is their ability to recognize proteins containing N-terminal (Nt) degradation signals called N-degrons, and to target these proteins for degradation by the 26S proteasome or autophagy. GID4, a subunit of the GID ubiquitin ligase, is the main recognition component of the proline (Pro)/N-degron pathway. GID4 targets proteins through their Nt-Pro residue or a Pro at position 2, in the presence of specific downstream sequence motifs. Here we show that human GID4 can also recognize hydrophobic Nt-residues other than Pro. One example is the sequence Nt-IGLW, bearing Nt-Ile. Nt-IGLW binds to wild-type human GID4 with a $$K_d$$ of 16 μM, whereas the otherwise identical Nt-Pro–bearing sequence PGLW binds to GID4 more tightly, with a $$K_d$$ of 1.9 μM. Despite this difference in affinities of GID4 for Nt-IGLW vs. Nt-PGLW, we found that the GID4-mediated Pro/N-degron pathway of the yeast Saccharomyces cerevisiae can target an Nt-IGLW–bearing protein for rapid degradation. We solved crystal structures of human GID4 bound to a peptide bearing Nt-Ile or Nt-Val. We also altered specific residues of human GID4 and measured the affinities of resulting mutant GID4s for Nt-IGLW and Nt-PGLW, thereby determining relative contributions of specific GID4 residues to the GID4-mediated recognition of Nt-Pro vs. Nt-residues other than Pro. These and related results advance the understanding of targeting by the Pro/N-degron pathway and greatly expand the substrate recognition range of the GID ubiquitin ligase in both human and yeast cells.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); Natural Sciences and Engineering Research Council of Canada (NSERC); AbbVie; Bayer Pharma AG; Boehringer Ingelheim; Canada Foundation for Innovation (CFI); Eshelman Institute for Innovation; Ontario Genomics Institute (OGI); European Union; European Federation of Pharmaceutical Industries and Associations; Janssen; Merck; Novartis Pharma AG; Ontario Ministry of Research, Innovation, and Science; Pfizer; São Paulo Research Foundation (FAPESP); Takeda; Wellcome; National Natural Science Foundation of China (NSFC); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1642239

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 25 Vol. 117; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (118)

Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability Rao, Hai; Uhlmann, Frank; Nasmyth, Kim Nature, Vol. 410, Issue 6831 https://doi.org/10.1038/35073627	journal	April 2001
Analyzing N-terminal Arginylation through the Use of Peptide Arrays and Degradation Assays Wadas, Brandon; Piatkov, Konstantin I.; Brower, Christopher S. Journal of Biological Chemistry, Vol. 291, Issue 40 https://doi.org/10.1074/jbc.M116.747956	journal	August 2016
The Hsp70 chaperone Ssa1 is essential for catabolite induced degradation of the gluconeogenic enzyme fructose-1,6-bisphosphatase Juretschke, Jeannette; Menssen, Ruth; Sickmann, Albert Biochemical and Biophysical Research Communications, Vol. 397, Issue 3 https://doi.org/10.1016/j.bbrc.2010.05.123	journal	July 2010
The N-end rule pathway as a nitric oxide sensor controlling the levels of multiple regulators Hu, Rong-Gui; Sheng, Jun; Qi, Xin Nature, Vol. 437, Issue 7061 https://doi.org/10.1038/nature04027	journal	October 2005
The endoplasmic reticulum–residing chaperone BiP is short-lived and metabolized through N-terminal arginylation Shim, Sang Mi; Choi, Ha Rim; Sung, Ki Woon Science Signaling, Vol. 11, Issue 511 https://doi.org/10.1126/scisignal.aan0630	journal	January 2018
DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk Justa-Schuch, Daniela; Silva-Garcia, Maria; Pilla, Esther eLife, Vol. 5 https://doi.org/10.7554/eLife.16370	journal	September 2016
Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway Dong, Cheng; Zhang, Heng; Li, Li Nature Chemical Biology, Vol. 14, Issue 5 https://doi.org/10.1038/s41589-018-0036-1	journal	April 2018
Regulating the Regulators: Recent Revelations in the Control of E3 Ubiquitin Ligases Vittal, Vinayak; Stewart, Mikaela D.; Brzovic, Peter S. Journal of Biological Chemistry, Vol. 290, Issue 35 https://doi.org/10.1074/jbc.R115.675165	journal	July 2015
The type-2 N-end rule peptide recognition activity of Ubr11 ubiquitin ligase is required for the expression of peptide transporters Kitamura, Kenji; Fujiwara, Hidenobu FEBS Letters, Vol. 587, Issue 2 https://doi.org/10.1016/j.febslet.2012.11.028	journal	December 2012
The mammalian CTLH complex is an E3 ubiquitin ligase that targets its subunit muskelin for degradation Maitland, Matthew E. R.; Onea, Gabriel; Chiasson, Christopher A. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-46279-5	journal	July 2019
Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway Oh, Jang-Hyun; Hyun, Ju-Yeon; Varshavsky, Alexander Proceedings of the National Academy of Sciences, Vol. 114, Issue 22 https://doi.org/10.1073/pnas.1705898114	journal	May 2017
PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol Sekine, Shiori; Youle, Richard J. BMC Biology, Vol. 16, Issue 1 https://doi.org/10.1186/s12915-017-0470-7	journal	January 2018
Life and death of proteins after protease cleavage: protein degradation by the N-end rule pathway Dissmeyer, Nico; Rivas, Susana; Graciet, Emmanuelle New Phytologist, Vol. 218, Issue 3 https://doi.org/10.1111/nph.14619	journal	June 2017
The SPOT-synthesis technique Frank, Ronald Journal of Immunological Methods, Vol. 267, Issue 1 https://doi.org/10.1016/S0022-1759(02)00137-0	journal	September 2002
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Protein N-Terminal Processing: Substrate Specificity of Escherichia coli and Human Methionine Aminopeptidases Xiao, Qing; Zhang, Feiran; Nacev, Benjamin A. Biochemistry, Vol. 49, Issue 26 https://doi.org/10.1021/bi1005464	journal	July 2010
Control of Protein Quality and Stoichiometries by N-Terminal Acetylation and the N-End Rule Pathway Shemorry, Anna; Hwang, Cheol-Sang; Varshavsky, Alexander Molecular Cell, Vol. 50, Issue 4 https://doi.org/10.1016/j.molcel.2013.03.018	journal	May 2013
Understanding the Pro/N-end rule pathway Dougan, David A.; Varshavsky, Alexander Nature Chemical Biology, Vol. 14, Issue 5 https://doi.org/10.1038/s41589-018-0045-0	journal	April 2018
Degradation of the Gluconeogenic Enzymes Fructose-1,6-bisphosphatase and Malate Dehydrogenase Is Mediated by Distinct Proteolytic Pathways and Signaling Events Hung, Guo-Chiuan; Brown, C. Randell; Wolfe, Allison B. Journal of Biological Chemistry, Vol. 279, Issue 47 https://doi.org/10.1074/jbc.M404544200	journal	September 2004
First Things First: Vital Protein Marks by N-Terminal Acetyltransferases Aksnes, Henriette; Drazic, Adrian; Marie, Michaël Trends in Biochemical Sciences, Vol. 41, Issue 9 https://doi.org/10.1016/j.tibs.2016.07.005	journal	September 2016
RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone Chang, YoonJeung; Paramasivam, Murugan; Girgenti, Matthew J. Developmental Neurobiology https://doi.org/10.1002/dneu.20750	journal	January 2009
The Gid-complex: an emerging player in the ubiquitin ligase league Liu, Huaize; Pfirrmann, Thorsten Biological Chemistry, Vol. 400, Issue 11 https://doi.org/10.1515/hsz-2019-0139	journal	November 2019
Fructose-1,6-bisphosphatase, Malate Dehydrogenase, Isocitrate Lyase, Phosphoenolpyruvate Carboxykinase, Glyceraldehyde-3-phosphate Dehydrogenase, and Cyclophilin A are secreted in Saccharomyces cerevisiae grown in low glucose Giardina, Bennett J.; Chiang, Hui-Ling Communicative & Integrative Biology, Vol. 6, Issue 6 https://doi.org/10.4161/cib.27216	journal	November 2013
The Ubiquitin–Proteasome System of Saccharomyces cerevisiae Finley, Daniel; Ulrich, Helle D.; Sommer, Thomas Genetics, Vol. 192, Issue 2 https://doi.org/10.1534/genetics.112.140467	journal	October 2012
Neurodegeneration-Associated Protein Fragments as Short-Lived Substrates of the N-End Rule Pathway Brower, Christopher S.; Piatkov, Konstantin I.; Varshavsky, Alexander Molecular Cell, Vol. 50, Issue 2 https://doi.org/10.1016/j.molcel.2013.02.009	journal	April 2013
Emerging branches of the N-end rule pathways are revealing the sequence complexities of N-termini dependent protein degradation Eldeeb, Mohamed A.; Leitao, Luana C. A.; Fahlman, Richard P. Biochemistry and Cell Biology, Vol. 96, Issue 3 https://doi.org/10.1139/bcb-2017-0274	journal	June 2018
N-degron and C-degron pathways of protein degradation Varshavsky, Alexander Proceedings of the National Academy of Sciences, Vol. 116, Issue 2 https://doi.org/10.1073/pnas.1816596116	journal	January 2019
Proteasome Structure and Assembly Budenholzer, Lauren; Cheng, Chin Leng; Li, Yanjie Journal of Molecular Biology, Vol. 429, Issue 22 https://doi.org/10.1016/j.jmb.2017.05.027	journal	November 2017
A reference-based protein degradation assay without global translation inhibitors Oh, Jang-Hyun; Chen, Shun-Jia; Varshavsky, Alexander Journal of Biological Chemistry, Vol. 292, Issue 52 https://doi.org/10.1074/jbc.M117.814236	journal	November 2017
Defining the geometry of the two-component proteasome degron Inobe, Tomonao; Fishbain, Susan; Prakash, Sumit Nature Chemical Biology, Vol. 7, Issue 3 https://doi.org/10.1038/nchembio.521	journal	January 2011
Ribosomal Stalling During Translation: Providing Substrates for Ribosome-Associated Protein Quality Control Joazeiro, Claudio A. P. Annual Review of Cell and Developmental Biology, Vol. 33, Issue 1 https://doi.org/10.1146/annurev-cellbio-111315-125249	journal	October 2017
Ubiquitin signaling and autophagy Grumati, Paolo; Dikic, Ivan Journal of Biological Chemistry, Vol. 293, Issue 15 https://doi.org/10.1074/jbc.TM117.000117	journal	November 2017
The N-recognin UBR4 of the N-end rule pathway is required for neurogenesis and homeostasis of cell surface proteins Kim, Sung Tae; Lee, Yoon Jee; Tasaki, Takafumi PLOS ONE, Vol. 13, Issue 8 https://doi.org/10.1371/journal.pone.0202260	journal	August 2018
The Auto-Generated Fragment of the Usp1 Deubiquitylase Is a Physiological Substrate of the N-End Rule Pathway Piatkov, Konstantin I.; Colnaghi, Luca; Békés, Miklos Molecular Cell, Vol. 48, Issue 6 https://doi.org/10.1016/j.molcel.2012.10.012	journal	December 2012
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
The N-end rule pathway and regulation by proteolysis Varshavsky, Alexander Protein Science, Vol. 20, Issue 8 https://doi.org/10.1002/pro.666	journal	July 2011
REFMAC 5 for the refinement of macromolecular crystal structures Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911001314	journal	March 2011
N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals Hwang, C. -S.; Shemorry, A.; Varshavsky, A. Science, Vol. 327, Issue 5968 https://doi.org/10.1126/science.1183147	journal	January 2010
Ubc8p functions in catabolite degradation of fructose-1,6-bisphosphatase in yeast Schüle, Thomas; Rose, Matthias; Entian, Karl-Dieter The EMBO Journal, Vol. 19, Issue 10 https://doi.org/10.1093/emboj/19.10.2161	journal	May 2000
Vps34p Is Required for the Decline of Extracellular Fructose-1,6-bisphosphatase in the Vacuole Import and Degradation Pathway Alibhoy, Abbas A.; Giardina, Bennett J.; Dunton, Danielle D. Journal of Biological Chemistry, Vol. 287, Issue 39 https://doi.org/10.1074/jbc.M112.360412	journal	July 2012
Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling Shiber, Ayala; Döring, Kristina; Friedrich, Ulrike Nature, Vol. 561, Issue 7722 https://doi.org/10.1038/s41586-018-0462-y	journal	August 2018
N-terminal methionine excision of proteins creates tertiary destabilizing N-degrons of the Arg/N-end rule pathway Nguyen, Kha The; Kim, Jeong-Mok; Park, Sang-Eun Journal of Biological Chemistry, Vol. 294, Issue 12 https://doi.org/10.1074/jbc.RA118.006913	journal	January 2019
RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8α and ARMC8β are components of the CTLH complex Kobayashi, Nobuaki; Yang, Jun; Ueda, Atsuhisa Gene, Vol. 396, Issue 2 https://doi.org/10.1016/j.gene.2007.02.032	journal	July 2007
N-terminal arginylation generates a bimodal degron that modulates autophagic proteolysis Yoo, Young Dong; Mun, Su Ran; Ji, Chang Hoon Proceedings of the National Academy of Sciences, Vol. 115, Issue 12 https://doi.org/10.1073/pnas.1719110115	journal	March 2018
Twists and turns in ubiquitin-like protein conjugation cascades Schulman, Brenda A. Protein Science, Vol. 20, Issue 12 https://doi.org/10.1002/pro.750	journal	November 2011
The Vacuolar Import and Degradation Pathway Merges with the Endocytic Pathway to Deliver Fructose-1,6-bisphosphatase to the Vacuole for Degradation Brown, C. Randell; Wolfe, Allison B.; Cui, Dongying Journal of Biological Chemistry, Vol. 283, Issue 38 https://doi.org/10.1074/jbc.M709922200	journal	July 2008
Molecular Phylogeny of a RING E3 Ubiquitin Ligase, Conserved in Eukaryotic Cells and Dominated by Homologous Components, the Muskelin/RanBPM/CTLH Complex Francis, Ore; Han, Fujun; Adams, Josephine C. PLoS ONE, Vol. 8, Issue 10 https://doi.org/10.1371/journal.pone.0075217	journal	October 2013
MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation Jin, X.; Pan, Y.; Wang, L. Oncogenesis, Vol. 6, Issue 4 https://doi.org/10.1038/oncsis.2017.21	journal	April 2017
Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen Graciet, E.; Hu, R. -G.; Piatkov, K. Proceedings of the National Academy of Sciences, Vol. 103, Issue 9 https://doi.org/10.1073/pnas.0511224103	journal	February 2006
Ubiquitylation at the crossroads of development and disease Rape, Michael Nature Reviews Molecular Cell Biology, Vol. 19, Issue 1 https://doi.org/10.1038/nrm.2017.83	journal	September 2017
Vid30 is required for the association of Vid vesicles and actin patches in the vacuole import and degradation pathway Alibhoy, Abbas A.; Giardina, Bennett J.; Dunton, Danielle D. Autophagy, Vol. 8, Issue 1 https://doi.org/10.4161/auto.8.1.18104	journal	January 2012
SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress Szoradi, Tamas; Schaeff, Katharina; Garcia-Rivera, Enrique M. Molecular Cell, Vol. 70, Issue 6 https://doi.org/10.1016/j.molcel.2018.04.027	journal	June 2018
Functional Roles of the E3 Ubiquitin Ligase UBR5 in Cancer Shearer, R. F.; Iconomou, M.; Watts, C. K. W. Molecular Cancer Research, Vol. 13, Issue 12 https://doi.org/10.1158/1541-7786.MCR-15-0383	journal	October 2015
N-terminal acetylation and the N-end rule pathway control degradation of the lipid droplet protein PLIN2 Nguyen, Kha The; Lee, Chang-Seok; Mun, Sang-Hyeon Journal of Biological Chemistry, Vol. 294, Issue 1 https://doi.org/10.1074/jbc.RA118.005556	journal	November 2018
Regulated import and degradation of a cytosolic protein in the yeast vacuole Chiang, Hui-Ling; Schekman, Randy Nature, Vol. 350, Issue 6316 https://doi.org/10.1038/350313a0	journal	March 1991
Catabolite Degradation of Fructose-1,6-bisphosphatase in the Yeast Saccharomyces cerevisiae : A Genome-wide Screen Identifies Eight Novel GID Genes and Indicates the Existence of Two Degradation Pathways Regelmann, Jochen; Schüle, Thomas; Josupeit, Frank S. Molecular Biology of the Cell, Vol. 14, Issue 4 https://doi.org/10.1091/mbc.E02-08-0456	journal	April 2003
The N-End Rule Pathway Tasaki, Takafumi; Sriram, Shashikanth M.; Park, Kyong Soo Annual Review of Biochemistry, Vol. 81, Issue 1 https://doi.org/10.1146/annurev-biochem-051710-093308	journal	July 2012
Cdc48-independent proteasomal degradation coincides with a reduced need for ubiquitylation Gödderz, Daniela; Heinen, Christian; Marchese, Francesco P. Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep07615	journal	January 2015
RMND5 from Xenopus laevis Is an E3 Ubiquitin-Ligase and Functions in Early Embryonic Forebrain Development Pfirrmann, Thorsten; Villavicencio-Lorini, Pablo; Subudhi, Abinash K. PLOS ONE, Vol. 10, Issue 3 https://doi.org/10.1371/journal.pone.0120342	journal	March 2015
The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments Piatkov, K. I.; Brower, C. S.; Varshavsky, A. Proceedings of the National Academy of Sciences, Vol. 109, Issue 27 https://doi.org/10.1073/pnas.1207786109	journal	June 2012
Evolution of Substrates and Components of the Pro/N-Degron Pathway Chen, Shun-Jia; Melnykov, Artem; Varshavsky, Alexander Biochemistry, Vol. 59, Issue 4 https://doi.org/10.1021/acs.biochem.9b00953	journal	December 2019
Gid9, a second RING finger protein contributes to the ubiquitin ligase activity of the Gid complex required for catabolite degradation Braun, Bernhard; Pfirrmann, Thorsten; Menssen, Ruth FEBS Letters, Vol. 585, Issue 24 https://doi.org/10.1016/j.febslet.2011.10.038	journal	October 2011
Target Selection during Protein Quality Control Shao, Sichen; Hegde, Ramanujan S. Trends in Biochemical Sciences, Vol. 41, Issue 2 https://doi.org/10.1016/j.tibs.2015.10.007	journal	February 2016
Exploring the Topology of the Gid Complex, the E3 Ubiquitin Ligase Involved in Catabolite-induced Degradation of Gluconeogenic Enzymes Menssen, Ruth; Schweiggert, Jörg; Schreiner, Jens Journal of Biological Chemistry, Vol. 287, Issue 30 https://doi.org/10.1074/jbc.M112.363762	journal	May 2012
The Logic of the 26S Proteasome Collins, Galen Andrew; Goldberg, Alfred L. Cell, Vol. 169, Issue 5 https://doi.org/10.1016/j.cell.2017.04.023	journal	May 2017
Gates, Channels, and Switches: Elements of the Proteasome Machine Finley, Daniel; Chen, Xiang; Walters, Kylie J. Trends in Biochemical Sciences, Vol. 41, Issue 1 https://doi.org/10.1016/j.tibs.2015.10.009	journal	January 2016
Proteasome Activators Stadtmueller, Beth M.; Hill, Christopher P. Molecular Cell, Vol. 41, Issue 1 https://doi.org/10.1016/j.molcel.2010.12.020	journal	January 2011
Ubiquitination of newly synthesized proteins at the ribosome Wang, Feng; Canadeo, Larissa A.; Huibregtse, Jon M. Biochimie, Vol. 114 https://doi.org/10.1016/j.biochi.2015.02.006	journal	July 2015
The Yeast GID Complex, a Novel Ubiquitin Ligase (E3) Involved in the Regulation of Carbohydrate Metabolism Santt, Olivier; Pfirrmann, Thorsten; Braun, Bernhard Molecular Biology of the Cell, Vol. 19, Issue 8 https://doi.org/10.1091/mbc.E08-03-0328	journal	August 2008
Ubiquitin Ligases: Structure, Function, and Regulation Zheng, Ning; Shabek, Nitzan Annual Review of Biochemistry, Vol. 86, Issue 1 https://doi.org/10.1146/annurev-biochem-060815-014922	journal	June 2017
Historical landmarks of autophagy research Ohsumi, Yoshinori Cell Research, Vol. 24, Issue 1 https://doi.org/10.1038/cr.2013.169	journal	December 2013
Wnt-Dependent Inactivation of the Groucho/TLE Co-repressor by the HECT E3 Ubiquitin Ligase Hyd/UBR5 Flack, Joshua E.; Mieszczanek, Juliusz; Novcic, Nikola Molecular Cell, Vol. 67, Issue 2 https://doi.org/10.1016/j.molcel.2017.06.009	journal	July 2017
Identification of Novel Vesicles in the Cytosol to Vacuole Protein Degradation Pathway Huang, Pei-Hsin; Chiang, Hui-Ling Journal of Cell Biology, Vol. 136, Issue 4 https://doi.org/10.1083/jcb.136.4.803	journal	February 1997
The ubiquitin ligase Ubr4 controls stability of podocin/MEC-2 supercomplexes Rinschen, Markus M.; Bharill, Puneet; Wu, Xiongwu Human Molecular Genetics, Vol. 25, Issue 7 https://doi.org/10.1093/hmg/ddw016	journal	January 2016
An N-end rule pathway that recognizes proline and destroys gluconeogenic enzymes Chen, Shun-Jia; Wu, Xia; Wadas, Brandon Science, Vol. 355, Issue 6323 https://doi.org/10.1126/science.aal3655	journal	January 2017
The degradation signal in a short-lived protein Bachmair, Andreas; Varshavsky, Alexander Cell, Vol. 56, Issue 6 https://doi.org/10.1016/0092-8674(89)90635-1	journal	March 1989
Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway Kim, Jeong-Mok; Seok, Ok-Hee; Ju, Shinyeong Science, Vol. 362, Issue 6418 https://doi.org/10.1126/science.aat0174	journal	November 2018
Perilous journey: a tour of the ubiquitin–proteasome system Kleiger, Gary; Mayor, Thibault Trends in Cell Biology, Vol. 24, Issue 6 https://doi.org/10.1016/j.tcb.2013.12.003	journal	June 2014
The N-Terminal Methionine of Cellular Proteins as a Degradation Signal Kim, Heon-Ki; Kim, Ryu-Ryun; Oh, Jang-Hyun Cell, Vol. 156, Issue 1-2 https://doi.org/10.1016/j.cell.2013.11.031	journal	January 2014
Ubiquitin-dependent protein degradation at the yeast endoplasmic reticulum and nuclear envelope Zattas, Dimitrios; Hochstrasser, Mark Critical Reviews in Biochemistry and Molecular Biology, Vol. 50, Issue 1 https://doi.org/10.3109/10409238.2014.959889	journal	September 2014
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
In vivo aspects of protein folding and quality control Balchin, David; Hayer-Hartl, Manajit; Hartl, F. Ulrich Science, Vol. 353, Issue 6294 https://doi.org/10.1126/science.aac4354	journal	June 2016
Recognition of Client Proteins by the Proteasome Yu, Houqing; Matouschek, Andreas Annual Review of Biophysics, Vol. 46, Issue 1 https://doi.org/10.1146/annurev-biophys-070816-033719	journal	May 2017
GID4 in complex with VGLWKS peptide Dong, C.; Tempel, W.; Bountra, C. Worldwide Protein Data Bank https://doi.org/10.2210/pdb6wzz/pdb	text	January 2020
The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution Dantuma, Nico P.; Bott, Laura C. Frontiers in Molecular Neuroscience, Vol. 7 https://doi.org/10.3389/fnmol.2014.00070	journal	July 2014
Regulation of c-Raf Stability through the CTLH Complex McTavish, Christina; Bérubé-Janzen, Wesley; Wang, Xu International Journal of Molecular Sciences, Vol. 20, Issue 4 https://doi.org/10.3390/ijms20040934	journal	February 2019
Protein Quality Control Degradation in the Nucleus Enam, Charisma; Geffen, Yifat; Ravid, Tommer Annual Review of Biochemistry, Vol. 87, Issue 1 https://doi.org/10.1146/annurev-biochem-062917-012730	journal	June 2018
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Structural basis for dual specificity of yeast N-terminal amidase in the N-end rule pathway Kim, Min Kyung; Oh, Sun Joo; Lee, Byung-Gil Proceedings of the National Academy of Sciences, Vol. 113, Issue 44 https://doi.org/10.1073/pnas.1612620113	journal	October 2016
The N-end rule in bacteria Tobias, J.; Shrader, T.; Rocap, G. Science, Vol. 254, Issue 5036 https://doi.org/10.1126/science.1962196	journal	November 1991
The eukaryotic N-end rule pathway: conserved mechanisms and diverse functions Gibbs, Daniel J.; Bacardit, Jaume; Bachmair, Andreas Trends in Cell Biology, Vol. 24, Issue 10 https://doi.org/10.1016/j.tcb.2014.05.001	journal	October 2014
The multi-subunit GID/CTLH E3 ubiquitin ligase promotes cell proliferation and targets the transcription factor Hbp1 for degradation Lampert, Fabienne; Stafa, Diana; Goga, Algera eLife, Vol. 7 https://doi.org/10.7554/eLife.35528	journal	June 2018
Role of Bicaudal C1 in renal gluconeogenesis and its novel interaction with the CTLH complex Leal-Esteban, Lucia Carolina; Rothé, Benjamin; Fortier, Simon PLOS Genetics, Vol. 14, Issue 7 https://doi.org/10.1371/journal.pgen.1007487	journal	July 2018
Remodeling of a delivery complex allows ClpS-mediated degradation of N-degron substrates Rivera-Rivera, Izarys; Román-Hernández, Giselle; Sauer, Robert T. Proceedings of the National Academy of Sciences, Vol. 111, Issue 37 https://doi.org/10.1073/pnas.1414933111	journal	September 2014
Calpain-generated natural protein fragments as short-lived substrates of the N-end rule pathway Piatkov, Konstantin I.; Oh, Jang-Hyun; Liu, Yuan Proceedings of the National Academy of Sciences, Vol. 111, Issue 9 https://doi.org/10.1073/pnas.1401639111	journal	February 2014
In vivo half-life of a protein is a function of its amino-terminal residue Bachmair, A.; Finley, D.; Varshavsky, A. Science, Vol. 234, Issue 4773 https://doi.org/10.1126/science.3018930	journal	October 1986
Comparative proteomic analysis of transition of saccharomyces cerevisiae from glucose-deficient medium to glucose-rich medium Giardina, Bennett J.; Stanley, Bruce A.; Chiang, Hui-Ling Proteome Science, Vol. 10, Issue 1 https://doi.org/10.1186/1477-5956-10-40	journal	January 2012
GID4 in complex with IGLWKS peptide Dong, C.; Tempel, W.; Bountra, C. Worldwide Protein Data Bank https://doi.org/10.2210/pdb6wzx/pdb	text	January 2020
Discovery of Cellular Regulation by Protein Degradation Varshavsky, Alexander Journal of Biological Chemistry, Vol. 283, Issue 50 https://doi.org/10.1074/jbc.X800009200	journal	August 2008
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins Piatkov, Konstantin; Vu, Tri; Hwang, Cheol-Sang Microbial Cell, Vol. 2, Issue 10 https://doi.org/10.15698/mic2015.10.231	journal	October 2015
Gid10 as an alternative N-recognin of the Pro/N-degron pathway Melnykov, Artem; Chen, Shun-Jia; Varshavsky, Alexander Proceedings of the National Academy of Sciences, Vol. 116, Issue 32 https://doi.org/10.1073/pnas.1908304116	journal	July 2019
Structure and Function of the 26S Proteasome Bard, Jared A. M.; Goodall, Ellen A.; Greene, Eric R. Annual Review of Biochemistry, Vol. 87, Issue 1 https://doi.org/10.1146/annurev-biochem-062917-011931	journal	June 2018
The ubiquitin system Hershko, Avram; Ciechanover, Aaron; Varshavsky, Alexander Nature Medicine, Vol. 6, Issue 10 https://doi.org/10.1038/80384	journal	October 2000
Mechanisms and Functions of Spatial Protein Quality Control Sontag, Emily Mitchell; Samant, Rahul S.; Frydman, Judith Annual Review of Biochemistry, Vol. 86, Issue 1 https://doi.org/10.1146/annurev-biochem-060815-014616	journal	June 2017
RING-Between-RING E3 Ligases: Emerging Themes amid the Variations Dove, Katja K.; Klevit, Rachel E. Journal of Molecular Biology, Vol. 429, Issue 22 https://doi.org/10.1016/j.jmb.2017.08.008	journal	November 2017
Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly Qiao, Shuai; Langlois, Christine R.; Chrustowicz, Jakub Molecular Cell, Vol. 77, Issue 1 https://doi.org/10.1016/j.molcel.2019.10.009	journal	January 2020
Vacuole import and degradation pathway: Insights into a specialized autophagy pathway Alibhoy, Abbas A. World Journal of Biological Chemistry, Vol. 2, Issue 11 https://doi.org/10.4331/wjbc.v2.i11.239	journal	January 2011
Structure of the human 26S proteasome at a resolution of 3.9 Å Schweitzer, Andreas; Aufderheide, Antje; Rudack, Till Proceedings of the National Academy of Sciences, Vol. 113, Issue 28 https://doi.org/10.1073/pnas.1608050113	journal	June 2016
The Cys-Arg/N-End Rule Pathway Is a General Sensor of Abiotic Stress in Flowering Plants Vicente, Jorge; Mendiondo, Guillermina M.; Movahedi, Mahsa Current Biology, Vol. 27, Issue 20 https://doi.org/10.1016/j.cub.2017.09.006	journal	October 2017
Degradation of Serotonin N -Acetyltransferase, a Circadian Regulator, by the N-end Rule Pathway Wadas, Brandon; Borjigin, Jimo; Huang, Zheping Journal of Biological Chemistry, Vol. 291, Issue 33 https://doi.org/10.1074/jbc.M116.734640	journal	June 2016
Biochemical Analysis of Fructose-1,6-bisphosphatase Import into Vacuole Import and Degradation Vesicles Reveals a Role for UBC1 in Vesicle Biogenesis Shieh, Hui-Ling; Chen, Yong; Brown, C. Randell Journal of Biological Chemistry, Vol. 276, Issue 13 https://doi.org/10.1074/jbc.M001767200	journal	December 2000
The N-end rule pathway: From recognition by N-recognins, to destruction by AAA+proteases Dougan, D. A.; Micevski, D.; Truscott, K. N. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1823, Issue 1 https://doi.org/10.1016/j.bbamcr.2011.07.002	journal	January 2012
Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development Weaver, Benjamin P.; Weaver, Yi M.; Mitani, Shohei Developmental Cell, Vol. 41, Issue 6 https://doi.org/10.1016/j.devcel.2017.05.013	journal	June 2017
ClpS is the recognition component for Escherichia coli substrates of the N-end rule degradation pathway Schmidt, Ronny; Zahn, Regina; Bukau, Bernd Molecular Microbiology, Vol. 72, Issue 2 https://doi.org/10.1111/j.1365-2958.2009.06666.x	journal	April 2009
‘Spalog’ and ‘sequelog’: neutral terms for spatial and sequence similarity Varshavsky, Alexander Current Biology, Vol. 14, Issue 5 https://doi.org/10.1016/j.cub.2004.02.014	journal	March 2004
Vid24p, a Novel Protein Localized to the Fructose-1,6-bisphosphatase–containing Vesicles, Regulates Targeting of Fructose-1,6-bisphosphatase from the Vesicles to the Vacuole for Degradation Chiang, Meng-Chieh; Chiang, Hui-Ling Journal of Cell Biology, Vol. 140, Issue 6 https://doi.org/10.1083/jcb.140.6.1347	journal	March 1998
Regulation of the Gid ubiquitin ligase recognition subunit Gid4 Menssen, Ruth; Bui, Kim; Wolf, Dieter H. FEBS Letters, Vol. 592, Issue 19 https://doi.org/10.1002/1873-3468.13229	journal	September 2018
Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism Lahiri, Vikramjit; Hawkins, Wayne D.; Klionsky, Daniel J. Cell Metabolism, Vol. 29, Issue 4 https://doi.org/10.1016/j.cmet.2019.03.003	journal	April 2019

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Title: Recognition of nonproline N-terminal residues by the Pro/N-degron pathway

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