Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions
Post-translational ubiquitination is an essential mechanism for the regulation of protein stability and function, which contributes to the regulation of the immune system. Cbl, an E3 ubiquitin ligase, is particularly well-characterized in the context of T and NK cell signaling, where it serves as a...
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MDPI AG
2024-12-01
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| author | Pulak Ranjan Nath Noah Isakov |
| author_facet | Pulak Ranjan Nath Noah Isakov |
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| description | Post-translational ubiquitination is an essential mechanism for the regulation of protein stability and function, which contributes to the regulation of the immune system. Cbl, an E3 ubiquitin ligase, is particularly well-characterized in the context of T and NK cell signaling, where it serves as a key regulator of receptor downstream signaling events and as a modulator of cell activation. Cbl promotes the proteasomal degradation of TCR/CD3 subunits as well as the protein kinases Fyn and Lck in T cells. Additionally, the scaffold protein linker for activation of T cells (LAT) is a universal target for Cbl-mediated ubiquitination and degradation in both T and NK cells. Recent findings suggest that CrkII-mediated ubiquitination and degradation of C3G by Cbl during early T cell activation may also be relevant to NK cell signaling. Given its role in modulating immune responses and its manageable impact on autoimmunity, Cbl is being investigated as a target for cancer immunotherapy. This review explores the ubiquitin ligase activity of Cbl and its implications for CAR T and NK cell immunotherapies. |
| format | Article |
| id | doaj-art-eecd5371d8be4cef86e0680581ae2378 |
| institution | DOAJ |
| issn | 2075-1729 |
| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-eecd5371d8be4cef86e0680581ae23782025-08-20T02:53:44ZengMDPI AGLife2075-17292024-12-011412159210.3390/life14121592Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell FunctionsPulak Ranjan Nath0Noah Isakov1Lentigen Technology Inc., A Miltenyi Biotec Company, 910 Clopper Road, Gaithersburg, MD 20878, USAThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, IsraelPost-translational ubiquitination is an essential mechanism for the regulation of protein stability and function, which contributes to the regulation of the immune system. Cbl, an E3 ubiquitin ligase, is particularly well-characterized in the context of T and NK cell signaling, where it serves as a key regulator of receptor downstream signaling events and as a modulator of cell activation. Cbl promotes the proteasomal degradation of TCR/CD3 subunits as well as the protein kinases Fyn and Lck in T cells. Additionally, the scaffold protein linker for activation of T cells (LAT) is a universal target for Cbl-mediated ubiquitination and degradation in both T and NK cells. Recent findings suggest that CrkII-mediated ubiquitination and degradation of C3G by Cbl during early T cell activation may also be relevant to NK cell signaling. Given its role in modulating immune responses and its manageable impact on autoimmunity, Cbl is being investigated as a target for cancer immunotherapy. This review explores the ubiquitin ligase activity of Cbl and its implications for CAR T and NK cell immunotherapies.https://www.mdpi.com/2075-1729/14/12/1592Cblubiquitinsignal transductionproteasomal degradationT cellNK cell |
| spellingShingle | Pulak Ranjan Nath Noah Isakov Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions Life Cbl ubiquitin signal transduction proteasomal degradation T cell NK cell |
| title | Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions |
| title_full | Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions |
| title_fullStr | Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions |
| title_full_unstemmed | Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions |
| title_short | Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions |
| title_sort | mechanisms of cbl mediated ubiquitination of proteins in t and natural killer cells and effects on immune cell functions |
| topic | Cbl ubiquitin signal transduction proteasomal degradation T cell NK cell |
| url | https://www.mdpi.com/2075-1729/14/12/1592 |
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