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E3 ubiquitin ligases as T cell anergy factors
Abstract
E3 ubiquitin ligases have emerged as key molecular regulators of immune cell function. Three families of proteins with ubiquitin ligase activity have been described (the HECT, RING and U-box proteins), and each may be involved in the regulation of immune responses during infection by targeting specific inhibitory molecules for proteolytic destruction. Several HECT and RING E3 proteins have now also been linked to the induction and maintenance of immune self-tolerance: c-Cbl, Cbl-b, GRAIL, Itch and Nedd4 each negatively regulate T cell growth factor production and proliferation. This review will discuss the relationship between the ubiquitination of select components of the antigen-sensing signaling apparatus in T cells and the development and maintenance of the clonal anergy state.
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“The E3 ubiquiting ligase family can affect PI3K, mTOR, and Ras/MAPK signaling pathways and help to actively maintain anergy [21,23,24].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [24]
Citations
Cites
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
The Immunological Synapse: A Molecular Machine Controlling T Cell Activation
Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M., & Dustin, M. L. (1999) · Science · doi:10.1126/science.285.5425.221 · Cited by 3,110
Three-dimensional segregation of supramolecular activation clusters in T cells
Monks, C. R. F., Freiberg, B. A., Kupfer, H., Sciaky, N., & Kupfer, A. (1998) · Nature · doi:10.1038/25764 · Cited by 2,353
Recognition of the polyubiquitin proteolytic signal
Thrower, J. S., Hoffman, L. M., Rechsteiner, M., & Pickart, C. M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.1.94 · Cited by 1,769
Harding, F., McArthur, J. G., Gross, J. A., Raulet, D. H., & Allison, J. P. (1992) · Nature · doi:10.1038/356607a0 · Cited by 1,558
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,507
Mueller, D. L., Jenkins, M. K., & Schwartz, R. H. (1989) · Annual Review of Immunology · doi:10.1146/annurev.iy.07.040189.002305 · Cited by 1,505
Self-citationSchwartz, R. H. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141110 · Cited by 1,487
Jenkins, M. K., & Schwartz, R. H. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.165.2.302 · Cited by 1,187
Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo.
Kearney, E. R., Pape, K., Loh, D., & Jenkins, M. (1994) · Immunity · doi:10.1016/1074-7613(94)90084-1 · Cited by 1,126
Liu, Y., Schiff, M., MARATHE, R. P., & Dinesh‐Kumar, S. P. (2002) · The Plant Journal · doi:10.1046/j.1365-313x.2002.01297.x · Cited by 1,043
The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase
Joazeiro, C. A. P., Wing, S. S., Huang, H.-K., Leverson, J. D., Hunter, T. R., & Liu, Y. (1999) · Science · doi:10.1126/science.286.5438.309 · Cited by 1,036
Winston, J. T., Strack, P. R., Beer‐Romero, P., Chu, C. Y., Elledge, S. J., & Harper, J. W. (1999) · Genes & Development · doi:10.1101/gad.13.3.270 · Cited by 964
c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptorPreprint
Levkowitz, G., Waterman, H., Zamir, E., Kam, Z., Oved, S., Langdon, W. Y., Beguinot, L., Geiger, B., & Yarden, Y. (1998) · Genes & Development · doi:10.1101/gad.12.23.3663 · Cited by 865
The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun
Jain, J., McCaffrey, P. G., Miner, Z., Kerppola, T. K., Jn, L., Verdine, G. L., Curran, T., & Rao, A. (1993) · Nature · doi:10.1038/365352a0 · Cited by 773
CDD: a curated Entrez database of conserved domain alignments
Marchler‐Bauer, A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg087 · Cited by 735
Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation
Haglund, K., Sigismund, S., Polo, S., Szymkiewicz, I., Di Fiore, P. P., & Dikic, I. (2003) · Nature Cell Biology · doi:10.1038/ncb983 · Cited by 715
Induction of Peripheral T Cell Tolerance In Vivo Requires CTLA-4 Engagement
Perez, V. L., Parijs, L. V., Biuckians, A., Zheng, X. X., Strom, T. B., & Abbas, A. K. (1997) · Immunity · doi:10.1016/s1074-7613(00)80284-8 · Cited by 715
CDART: Protein Homology by Domain ArchitecturePreprint
Geer, L. Y., Domrachev, M., Lipman, D. J., & Bryant, S. H. (2002) · Genome Research · doi:10.1101/gr.278202 · Cited by 702
Function of WW Domains as Phosphoserine- or Phosphothreonine-Binding Modules
Lu, P., Zhou, X. Z., Shen, M., & Lu, K. P. (1999) · Science · doi:10.1126/science.283.5406.1325 · Cited by 688
Transcriptional Mechanisms Underlying Lymphocyte Tolerance
Macián, F., Garcia-Cozar, F. J., Im, S., Horton, H. F., Byrne, M. C., & Rao, A. (2002) · Cell · doi:10.1016/s0092-8674(02)00767-5 · Cited by 687
Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b
Bachmaier, K., Krawczyk, C. M., Kozieradzki, I., Kong, Y., Sasaki, T., Oliveira-dos-Santos, A., Mariathasan, S., Bouchard, D., Wakeham, A. C., Itié, A., et al. (2000) · Nature · doi:10.1038/35003228 · Cited by 674
The Drosophila immune system detects bacteria through specific peptidoglycan recognition
Leulier, F., Parquet, C., Pili‐Floury, S., Ryu, J.-H., Caroff, M., Lee, W., Mengin‐Lecreulx, D., & Lemaître, B. (2003) · Nature Immunology · doi:10.1038/ni922 · Cited by 660
Identification of the receptor component of the IκBα–ubiquitin ligase
Yaron, A., Hatzubai, A., Davis, M., Lavon, I., Amit, S., Manning, A. M., Andersen, J., Mann, M., Mercurio, F., & Ben‐Neriah, Y. (1998) · Nature · doi:10.1038/25159 · Cited by 654
Cbl-b regulates the CD28 dependence of T-cell activation
Chiang, Y. J., Kole, H. K., Brown, K. E., Naramura, M., Fukuhara, S., Hu, R.-J., Jang, I. K., Gutkind, J. S., Shevach, E. M., & Gu, H. (2000) · Nature · doi:10.1038/35003235 · Cited by 626
Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination
Staub, O., Gautschi, I., Ishikawa, T., Breitschopf, K., Ciechanover, A., Schild, L., & Rotin, D. (1997) · The EMBO Journal · doi:10.1093/emboj/16.21.6325 · Cited by 601
Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins
Heissmeyer, V., Macián, F., Im, S., Varma, R., Feske, S., Venuprasad, K., Gu, H., Liu, Y., Dustin, M. L., & Rao, A. (2004) · Nature Immunology · doi:10.1038/ni1047 · Cited by 515
Ryals, J. A., Weymann, K. B., Lawton, K. A., Friedrich, L., Ellis, D., Steiner, H., Johnson, J. R., Delaney, T. P., Jesse, T., Vos, P., et al. (1997) · The Plant Cell · doi:10.1105/tpc.9.3.425 · Cited by 480
Signal-induced ubiquitination of Ikappa Balpha by the F-box protein Slimb/beta -TrCPPreprint
Spencer, E., Jiang, J., & Chen, Z. J. (1999) · Genes & Development · doi:10.1101/gad.13.3.284 · Cited by 436
Blocked Signal Transduction to the ERK and JNK Protein Kinases in Anergic CD4 + T Cells
Li, W., Whaley, C. D., Mondino, A., & Mueller, D. L. (1996) · Science · doi:10.1126/science.271.5253.1272 · Cited by 427
Self-citationMaintenance of Human T Cell Anergy: Blocking of IL-2 Gene Transcription by Activated Rap1
Boussiotis, V. A., Freeman, G. J., Berezovskaya, A., Barber, D. L., & Nadler, L. M. (1997) · Science · doi:10.1126/science.278.5335.124 · Cited by 408
c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation
Naramura, M., Jang, I. K., Kole, H. K., Huang, F., Haines, D. C., & Gu, H. (2002) · Nature Immunology · doi:10.1038/ni855 · Cited by 396
Quill, H., & Schwartz, R. H. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.138.11.3704 · Cited by 388
The Rel Protein DIF Mediates the Antifungal but Not the Antibacterial Host Defense in Drosophila
Rutschmann, S., Jung, A. C., Hétru, C., Reichhart, J., Hoffmann, J. A., & Ferrandon, D. (2000) · Immunity · doi:10.1016/s1074-7613(00)80208-3 · Cited by 377
Blocked Ras Activation in Anergic CD4 + T Cells
Fields, P. E., Gajewski, T. F., & Fitch, F. W. (1996) · Science · doi:10.1126/science.271.5253.1276 · Cited by 370
Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice
Murphy, M. A., Schnall, R., Venter, D. J., Barnett, L. D., Bertoncello, I., Thien, C. B. F., Langdon, W. Y., & Bowtell, D. D. L. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4872 · Cited by 361
Liu, Y., Schiff, M., Serino, G., Deng, X., & Dinesh‐Kumar, S. P. (2002) · The Plant Cell · doi:10.1105/tpc.002493 · Cited by 346
Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation
Fang, D., Elly, C., Gao, B., Fang, N., Altman, Y., Joazeiro, C. A. P., Hunter, T. R., Copeland, N. G., Jenkins, N. A., & Liu, Y. (2002) · Nature Immunology · doi:10.1038/ni763 · Cited by 341
Altered thymic positive selection and intracellular signals in Cbl-deficient mice
Naramura, M., Kole, H. K., Hu, R.-J., & Gu, H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15547 · Cited by 337
Reversal of in vitro T cell clonal anergy by IL-2 stimulation
Beverly, B., Kang, S., Lenardo, M. J., & Schwartz, R. H. (1992) · International Immunology · doi:10.1093/intimm/4.6.661 · Cited by 333
Recognition and Ubiquitination of Notch by Itch, a Hect-type E3 Ubiquitin Ligase
Qiu, L., Joazeiro, C. A. P., Fang, N., Wang, H., Elly, C., Altman, Y., Fang, D., Hunter, T. R., & Liu, Y. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007300200 · Cited by 332
Transactivation by AP-1 Is a Molecular Target of T Cell Clonal Anergy
Kang, S., Beverly, B., Tran, A.-C., Brorson, K., Schwartz, R. H., & Lenardot, M. J. (1992) · Science · doi:10.1126/science.257.5073.1134 · Cited by 318
v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas.
Langdon, W. Y., Hartley, J. W., Klinken, S. P., Ruscetti, S. K., & Morse, H. C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.4.1168 · Cited by 308
Jenkins, M. K., Pardoll, D. M., Mizuguchi, J., Chused, T. M., & Schwartz, R. H. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.15.5409 · Cited by 298
Powell, J. D., Lerner, C. G., & Schwartz, R. H. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.5.2775 · Cited by 290
Anandasabapathy (2003) · doi:10.1016/s1074-7613(03)00084-0 · Cited by 285
Proteolysis-independent regulation of PI3K by Cbl-b–mediated ubiquitination in T cells
Fang, D., & Liu, Y. (2001) · Nature Immunology · doi:10.1038/ni0901-870 · Cited by 279
Sebzda, E., Bracke, M., Tugal, T., Hogg, N., & Cantrell, D. A. (2002) · Nature Immunology · doi:10.1038/ni765 · Cited by 275
Clonal anergy is induced in vitro by T cell receptor occupancy in the absence of proliferation
DeSilva, D. R., Urdahl, K. B., & Jenkins, M. K. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.10.3261 · Cited by 252
Blake, T. J. A., Shapiro, M., Morse, H. C., & Langdon, W. Y. (1991) · PubMed · Cited by 235
Hatakeyama, S., Kitagawa, M., Nakayama, K., Shirane, M., Matsumoto, M., Hattori, K., Higashi, H., Nakano, H., Okumura, K., Onoé, K., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3859 · Cited by 202
Pape, K. A., Merica, R. R., Mondino, A., Khoruts, A., & Jenkins, M. K. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.10.4719 · Cited by 192
Cblb is a major susceptibility gene for rat type 1 diabetes mellitus
Yokoi, N., Komeda, K., Wang, H., Yano, H., Kitada, K., Saitoh, Y., Seino, Y., Yasuda, K., Serikawa, T., & Seino, S. (2002) · Nature Genetics · doi:10.1038/ng927 · Cited by 176
Cbl Promotes Ubiquitination of the T Cell Receptor ζ through an Adaptor Function of Zap-70
Wang, H.-Y., Altman, Y., Fang, D., Elly, C., Dai, Y., Shao, Y., & Liu, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010738200 · Cited by 168
Two isoforms of otubain 1 regulate T cell anergy via GRAIL
Soares, L. R. B., Seroogy, C. M., Skrenta, H., Anandasabapathy, N., Lovelace, P. A., Chung, C. D., Engleman, E. G., & Fathman, C. G. (2003) · Nature Immunology · doi:10.1038/ni1017 · Cited by 167
WW Domain HECT E3s Target Cbl RING Finger E3s for Proteasomal Degradation
Magnifico, A., Ettenberg, S. A., Yang, C., Mariano, J. M., Tiwari, S., Fang, S., Lipkowitz, S., & Weissman, A. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308009200 · Cited by 161
Imhof, M. O., & McDonnell, D. P. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.2594 · Cited by 159
Zhang, J., Bárdos, T., Li, D., Gál, I., Vermes, C., Xu, J., Mikecz, K., Finnegan, A., Lipkowitz, S., & Glant, T. T. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.5.2236 · Cited by 155
Gajewski, T. F., Qian, D., Fields, P. E., & Fitch, F. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.1.38 · Cited by 130
Tanchot, C., Barber, D. L., Chiodetti, L., & Schwartz, R. H. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.4.2030 · Cited by 124
DeSilva, D. R., Feeser, W. S., Tancula, E. J., & Scherle, P. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.5.2017 · Cited by 121
Angers, A., Ramjaun, A. R., & McPherson, P. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309934200 · Cited by 118
Mondino, A., Whaley, C. D., DeSilva, D. R., Li, W., Jenkins, M. K., & Mueller, D. L. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.2048 · Cited by 112
Self-citationCulprits in the degradation of cyclin E apprehendedPreprint
Winston, J. T., Chu, C., & Harper, J. W. (1999) · Genes & Development · doi:10.1101/gad.13.21.2751 · Cited by 82
Vanasek, T. L., Khoruts, A., Zell, T., & Mueller, D. L. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5636 · Cited by 79
Self-citationZhang, W., Shao, Y., Fang, D., Huang, J., Jeon, M., & Liu, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212671200 · Cited by 78
Reduced CD3-mediated protein tyrosine phosphorylation in anergic CD4+ and CD8+ T cells.
Bhandoola, A., Cho, E. A., Yui, K., Saragovi, H., Greene, M. I., & Quill, H. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.5.2355 · Cited by 67
Structural basis of ubiquitylation
VanDemark, A. P. (2002) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(02)00389-5 · Cited by 64
Leulier, F., Marchal, C., Miletich, I., Limbourg-Bouchon, B., Benarous, R., & Lemaître, B. (2003) · EMBO Reports · doi:10.1038/sj.embor.embor936 · Cited by 59
Evidence for Repression of IL-2 Gene Activation in Anergic T Cells
Telander, D. G., Malvey, E.-N., & Mueller, D. L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1460 · Cited by 53
Self-citationNegative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase
Shao, Y., Elly, C., & Liu, Y. (2003) · EMBO Reports · doi:10.1038/sj.embor.embor813 · Cited by 36
Dillon, T. J., Karpitski, V., Wetzel, S. A., Parker, D. C., Shaw, A. S., & Stork, P. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301506200 · Cited by 30
The E3 Ubiquitin Ligase GREUL1 Anteriorizes Ectoderm during Xenopus Development
Borchers, A., Hufton, A. L., Eldridge, A. G., Jackson, P. K., Harland, R. M., & Baker, J. C. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0814 · Cited by 30
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Research works printed but not linked: 1
- Ryals, J. et al. The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor IκB. Plant Cell 9, 425–439 (1997).
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Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
PD-1 and PD-1 ligands: from discovery to clinical application
Okazaki, T., & Honjo, T. (2007) · International Immunology · doi:10.1093/intimm/dxm057 · Cited by 1,310
The Continuing Challenges of Leprosy
Scollard, D. M., Adams, L. B., Gillis, T., Krahenbuhl, J. L., Truman, R. W., & Williams, D. L. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.19.2.338-381.2006 · Cited by 947
“Recent work has revealed some mechanisms by which this pathway regulates the processing of protein antigens within macrophages, thereby affecting antigen presentation to lymphocytes and the resulting immune response (278, 429).”
BackgroundT cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
Crespo, J., Sun, H., Welling, T. H., Tian, Z., & Zou, W. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.12.003 · Cited by 752
“The E3 ubiquiting ligase family can affect PI3K, mTOR, and Ras/MAPK signaling pathways and help to actively maintain anergy [21,23,24].”
BackgroundMolecular and Transcriptional Basis of CD4+ T Cell Dysfunction during Chronic Infection
Crawford, A., Angelosanto, J., Kao, C., Doering, T. A., Odorizzi, P. M., Barnett, B. E., & Wherry, E. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.005 · Cited by 513
Metadata
- Authors
- Mueller, D. L.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Mueller, Daniel L
- ORCID
- Mueller, Daniel L
- Venue
- Nature Immunology
- Published
- 2004-08-27
- Volume
- 5
- Issue
- 9
- Pages
- 883-890
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2005935110
- Cited by
- 224
- References
- 73
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 14 · 2013: 11 · 2012: 7
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01 GM54706, R01GM054706)
- National Institute of Allergy and Infectious Diseases (P01AI50162, P01-AI 35296, P01AI050162, P01AI035296)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- E3 ubiquitin ligase, T cell anergy, HECT E3 ligases, RING E3 ligases, ubiquitination, self-tolerance, c-Cbl, Cbl-b, GRAIL, pruritus, NEDD4, T cell proliferation
- MeSH terms
- Animals, Humans, T-Lymphocytes, Signal Transduction, Self Tolerance, Clonal Anergy, Models, Immunological, Ubiquitin-Protein Ligases
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