The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans
Open accessAbstract
Experimental manipulation of protein abundance in living cells or organisms is an essential strategy for investigation of biological regulatory mechanisms. While powerful techniques for protein expression have been developed in C. elegans, existing tools for conditional disruption of protein function are far more limited. To address this, we have adapted the auxin-inducible degradation (AID) system discovered in plants to enable conditional protein depletion in C. elegans. We report that expression of a modified Arabidopsis TIR1 F-box protein mediates robust auxin-dependent depletion of degron-tagged targets. We document the effectiveness of this system for depletion of nuclear and cytoplasmic proteins in diverse somatic and germline tissues throughout development. Target proteins were depleted in as little as 20-30 minutes, and their expression could be reestablished upon auxin removal. We have engineered strains expressing TIR1 under the control of various promoter and 3' UTR sequences to drive tissue-specific or temporally regulated expression. The degron tag can be efficiently introduced by CRISPR/Cas9-based genome editing. We have harnessed this system to explore the roles of dynamically expressed nuclear hormone receptors in molting, and to analyze meiosis-specific roles for proteins required for germline proliferation. Together, our results demonstrate that the AID system provides a powerful new tool for spatiotemporal regulation and analysis of protein function in a metazoan model organism.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456
The F-box protein TIR1 is an auxin receptor
Dharmasiri, N., Dharmasiri, S., & Estelle, M. (2005) · Nature · doi:10.1038/nature03543 · Cited by 2,083
The Arabidopsis F-box protein TIR1 is an auxin receptor
Kepinski, S., & Leyser, O. (2005) · Nature · doi:10.1038/nature03542 · Cited by 1,714
Mechanism of auxin perception by the TIR1 ubiquitin ligase
Tan, X., Calderon-Villalobos, L. I. A., Sharon, M., Zheng, C., Robinson, C. V., Estelle, M., & Zheng, N. (2007) · Nature · doi:10.1038/nature05731 · Cited by 1,688
An auxin-based degron system for the rapid depletion of proteins in nonplant cells
Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T., & Kanemaki, M. (2009) · Nature Methods · doi:10.1038/nmeth.1401 · Cited by 1,663
Single-copy insertion of transgenes in Caenorhabditis elegans
Frøkjær-Jensen, C., Wayne Davis, M., Hopkins, C. E., Newman, B. J., Thummel, J. M., Olesen, S.-P., Grunnet, M., & Jorgensen, E. M. (2008) · Nature Genetics · doi:10.1038/ng.248 · Cited by 1,163
Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination
Dickinson, D. J., Ward, J. D., Reiner, D. J., & Goldstein, B. (2013) · Nature Methods · doi:10.1038/nmeth.2641 · Cited by 957
Self-citationBanaszynski, L. A., Chen, L.-C., Maynard-Smith, L. A., Ooi, A. G. L., & Wandless, T. J. (2006) · Cell · doi:10.1016/j.cell.2006.07.025 · Cited by 902
Arribere, J. A., Bell, R. T., Fu, B. X. H., Artiles, K. L., Hartman, P. S., & Fire, A. Z. (2014) · Genetics · doi:10.1534/genetics.114.169730 · Cited by 794
Ruegger, M., Dewey, E., Gray, W. M., Hobbie, L., Turner, J., & Estelle, M. (1998) · Genes & Development · doi:10.1101/gad.12.2.198 · Cited by 669
Streamlined Genome Engineering with a Self-Excising Drug Selection Cassette
Dickinson, D. J., Pani, A. M., Heppert, J. K., Higgins, C. D., & Goldstein, B. (2015) · Genetics · doi:10.1534/genetics.115.178335 · Cited by 586
Gray, W. M., del Pozo, J. C., Walker, L., Hobbie, L., Risseeuw, E., Banks, T., Crosby, W. L., Yang, M., Ma, H., & Estelle, M. (1999) · Genes & Development · doi:10.1101/gad.13.13.1678 · Cited by 525
Fluorescent fusion protein knockout mediated by anti-GFP nanobody
Caussinus, E., Kanca, O., & Affolter, M. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2180 · Cited by 510
An expanded tool kit for the auxin‐inducible degron system in budding yeast
Morawska, M., & Ulrich, H. D. (2013) · Yeast · doi:10.1002/yea.2967 · Cited by 429
Malone, C. J., Misner, L., Le Bot, N., Tsai, M.-C., Campbell, J. M., Ahringer, J., & White, J. G. (2003) · Cell · doi:10.1016/s0092-8674(03)00985-1 · Cited by 401
MacQueen, A. J., Colaiácovo, M. P., McDonald, K., & Villeneuve, A. M. (2002) · Genes & Development · doi:10.1101/gad.1011602 · Cited by 388
Heat-Inducible Degron: a Method for Constructing Temperature-Sensitive Mutants
Dohmen, R. J., Wu, P., & Varshavsky, A. (1994) · Science · doi:10.1126/science.8122109 · Cited by 347
Chromosome Sites Play Dual Roles to Establish Homologous Synapsis during Meiosis in C. elegans
MacQueen, A. J., Phillips, C. M., Bhalla, N., Weiser, P., Villeneuve, A. M., & Dernburg, A. F. (2005) · Cell · doi:10.1016/j.cell.2005.09.034 · Cited by 315
Self-citationGlobal analysis of dauer gene expression in Caenorhabditis elegans
Wang, J., & Kim, S. K. (2003) · Development · doi:10.1242/dev.00363 · Cited by 310
Inducible, reversible system for the rapid and complete degradation of proteins in mammalian cells
Holland, A. J., Fachinetti, D., Han, J. S., & Cleveland, D. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216880109 · Cited by 303
A Co-CRISPR Strategy for Efficient Genome Editing in Caenorhabditis elegans
Kim, H., Ishidate, T., Ghanta, K. S., Seth, M., Conte, D., Shirayama, M., & Mello, C. C. (2014) · Genetics · doi:10.1534/genetics.114.166389 · Cited by 294
Cytoskeletal Forces Span the Nuclear Envelope to Coordinate Meiotic Chromosome Pairing and Synapsis
Sato, A., Isaac, B., Phillips, C. M., Rillo, R., Carlton, P. M., Wynne, D. J., Kasad, R. A., & Dernburg, A. F. (2009) · Cell · doi:10.1016/j.cell.2009.10.039 · Cited by 285
Self-citationPaix, A., Wang, Y., Smith, H. E., Lee, C.-Y. S., Calidas, D., Lu, T., Smith, J., Schmidt, H., Krause, M. W., & Seydoux, G. (2014) · Genetics · doi:10.1534/genetics.114.170423 · Cited by 282
A LOV2 Domain-Based Optogenetic Tool to Control Protein Degradation and Cellular Function
Renicke, C., Schuster, D., Usherenko, S., Essen, L.-O., & Taxis, C. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.03.005 · Cited by 247
Establishment of a tissue-specific RNAi system in C. elegans
Qadota, H., Inoue, M., Hikita, T., Köppen, M., Hardin, J. D., Amano, M., Moerman, D. G., & Kaibuchi, K. (2007) · Gene · doi:10.1016/j.gene.2007.06.020 · Cited by 213
Ward, J. D. (2015) · Genetics · doi:10.1534/genetics.114.172361 · Cited by 207
Self-citationSmall-molecule displacement of a cryptic degron causes conditional protein degradation
Bonger, K. M., Chen, L.-C., Liu, C. W., & Wandless, T. J. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.598 · Cited by 206
Harnessing the Ubiquitination Machinery to Target the Degradation of Specific Cellular Proteins
Zhou, P., Bogacki, R., McReynolds, L., & Howley, P. M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00074-5 · Cited by 164
A P-glycoprotein protects Caenorhabditis elegans against natural toxins.
Broeks, A., Janssen, H. W., Calafat, J., & Plasterk, R. H. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07178.x · Cited by 161
Shen, Z., Zhang, X., Chai, Y., Zhu, Z., Yi, P., Feng, G., Li, W., & Ou, G. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.07.017 · Cited by 155
Gene Activation Using FLP Recombinase in C. elegans
Davis, M. W., Morton, J. J., Carroll, D., & Jørgensen, E. M. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000028 · Cited by 132
The Caenorhabditis elegans Skp1-Related Gene Family
Nayak, S., Santiago, F. E., Jin, H., Lin, D., Schedl, T., & Kipreos, E. T. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00682-6 · Cited by 131
Dynein-dependent processive chromosome motions promote homologous pairing in C. elegans meiosis
Wynne, D. J., Rog, O., Carlton, P. M., & Dernburg, A. F. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201106022 · Cited by 131
Self-citationKostrouchová, M., Krause, M., Kostrouch, Z., & Rall, J. E. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131171898 · Cited by 129
Repurposing an endogenous degradation system for rapid and targeted depletion of C. elegans proteins
Armenti, S. T., Lohmer, L. L., Sherwood, D. R., & Nance, J. (2014) · Development · doi:10.1242/dev.115048 · Cited by 124
Wei, X., Potter, C. J., Luo, L., & Shen, K. (2012) · Nature Methods · doi:10.1038/nmeth.1929 · Cited by 120
Philip, N., & Waters, A. P. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.05.018 · Cited by 114
Acute Drug Treatment in the Early C. elegans Embryo
Carvalho, A. X., Olson, S. K., Gutierrez, E., Zhang, K., Earnest-Noble, L. B., Zanin, E., Desai, A. B., Groisman, A., & Oegema, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024656 · Cited by 114
Efficient protein depletion by genetically controlled deprotection of a dormant N‐degron
Taxis, C., Stier, G., Spadaccini, R., & Knop, M. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.25 · Cited by 103
Zhou, K., Rolls, M. M., Hall, D. H., Malone, C. J., & Hanna‐Rose, W. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200902101 · Cited by 93
Cytological Analysis of Meiosis in Caenorhabditis elegans
Phillips, C. M., McDonald, K. L., & Dernburg, A. F. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-103-5_11 · Cited by 91
Self-citationAuxin-inducible protein depletion system in fission yeast
Kanke, M., Nishimura, K., Kanemaki, M. T., Kakimoto, T., Takahashi, T. S., Nakagawa, T., & Masukata, H. (2011) · BMC Cell Biology · doi:10.1186/1471-2121-12-8 · Cited by 88
Direct Visualization Reveals Kinetics of Meiotic Chromosome Synapsis
Rog, O., & Dernburg, A. F. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.032 · Cited by 88
Self-citationEfficient Genome Editing in Caenorhabditis elegans with a Toolkit of Dual-Marker Selection Cassettes
Norris, A. D., Kim, H., Colaiácovo, M. P., & Calarco, J. A. (2015) · Genetics · doi:10.1534/genetics.115.180679 · Cited by 84
Chemical Inducers of Targeted Protein Degradation
Raina, K., & Crews, C. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.078105 · Cited by 66
Yu, H. J., Moss, B. L., Jang, S.-H., Prigge, M. J., Klavins, E., Nemhauser, J. L., & Estelle, M. A. (2013) · PLANT PHYSIOLOGY · doi:10.1104/pp.113.215582 · Cited by 64
Temporal Control of Cell-Specific Transgene Expression in Caenorhabditis elegans
Bacaj, T., & Shaham, S. (2007) · Genetics · doi:10.1534/genetics.107.074369 · Cited by 62
Rapid and Tunable Control of Protein Stability in Caenorhabditis elegans Using a Small Molecule
Cho, U. H., Zimmerman, S. M., Chen, L., Owen, E., Kim, J. V., Kim, S. K., & Wandless, T. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072393 · Cited by 53
The Caenorhabditis elegans Nuclear Receptor Gene nhr-25 Regulates Epidermal Cell Development
Chen, Z., Eastburn, D. J., & Han, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.17.7345-7358.2004 · Cited by 52
2A and the Auxin-Based Degron System Facilitate Control of Protein Levels in Plasmodium falciparum
Kreidenweiss, A., Hopkins, A. V., & Mordmüller, B. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078661 · Cited by 44
Asahina, M., Valenta, T., Macůrková, M., Kořínek, V., & Jindra, M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.06.003 · Cited by 42
Conditional targeted genome editing using somatically expressed TALENs in C. elegans
Cheng, Z., Yi, P., Wang, X., Chai, Y., Feng, G., Yang, Y., Liang, X., Zhu, Z., Li, W., & Ou, G. (2013) · Nature Biotechnology · doi:10.1038/nbt.2674 · Cited by 41
Self-citationSumoylated NHR-25/NR5A Regulates Cell Fate during C. elegans Vulval Development
Ward, J. D., Bojanala, N., Bernal, T. U., Ashrafi, K., Asahina, M., & Yamamoto, K. R. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003992 · Cited by 35
Self-citation
Cited by
Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors
Natsume, T., Kiyomitsu, T., Saga, Y., & Kanemaki, M. T. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.001 · Cited by 673
Yesbolatova, A., Saito, Y., Kitamoto, N., Makino-Itou, H., Ajima, R., Nakano, R., Nakaoka, H., Fukui, K., Gamo, K., Tominari, Y., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19532-z · Cited by 533
Chemically induced proximity in biology and medicine
Stanton, B. Z., Chory, E. J., & Crabtree, G. R. (2018) · Science · doi:10.1126/science.aao5902 · Cited by 475
Small-Molecule Modulation of Protein Homeostasis
Burslem, G. M., & Crews, C. M. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00077 · Cited by 283
Shen, E.-Z., Chen, H., Ozturk, A. R., Tu, S., Shirayama, M., Tang, W., Ding, Y.-H., Dai, S.-Y., Weng, Z., & Mello, C. C. (2018) · Cell · doi:10.1016/j.cell.2018.02.002 · Cited by 226
Metadata
- Authors
- Zhang, L., Ward, J. D., Cheng, Z., & Dernburg, A. F.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2015-01-01
- Volume
- 142
- Issue
- 24
- Pages
- 4374-84
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2172886986
- Cited by
- 599
- References
- 54
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
