IL-15 in autoimmunity and cancer: O-tu-b or not O-tu-b?

@article{Moynagh2019IL15IA,
  title={IL-15 in autoimmunity and cancer: O-tu-b or not O-tu-b?},
  author={Paul N. Moynagh},
  journal={Nature Immunology},
  year={2019},
  volume={20},
  pages={780 - 782},
  url={https://api.semanticscholar.org/CorpusID:182952228}
}
A new study reveals the deubiquitinase Otub1 to be a negative regulator of IL-15 signaling, with important consequences for autoimmunity and anti-cancer immunity.
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3 Citations
Background Citations
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Results Citations
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11 References

IL-7– and IL-15–Mediated TCR Sensitization Enables T Cell Responses to Self-Antigens

It is proposed that HCs, possibly induced by lymphopenia, decrease the signaling threshold for TCR activation and are thereby partly responsible for autoimmunity in RA.

The deubiquitinase Otub1 controls the activation of CD8 T cells and NK cells by regulating IL-15-mediated priming

It is shown that IL-15 also mediates homeostatic priming of CD8+ T cells for antigen-stimulated activation, which is controlled by a deubiquitinase, Otub1, which controls the maturation and activation of NK cells.

Regulating the immune system via IL-15 transpresentation.

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The innate functions of CD8+ T‐cells and those of NK cells are compared and how these relate to expression of phenotypic markers, especially CD161 and CD56 are compared.

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The actions of γc family cytokines are discussed, their critical biological roles and signaling pathways, focusing mainly on JAK/STAT (signal transducers and activators of transcription) signaling, and how this information is now being used in clinical therapeutic efforts.

Otubain 1: a non-canonical deubiquitinase with an emerging role in cancer.

Interestingly, in addition to catalytic DUB activity, OTUB1 displays a catalytic-independent, non-canonical activity where it inhibits the transfer of ubiquitin onto protein substrates by sequestration of E2 ubiquit in-conjugating enzymes.

miR-542-3p inhibits colorectal cancer cell proliferation, migration and invasion by targeting OTUB1.

The study demonstrates the importance of miR-524-3p/OTUB1 signaling in CRC development and suggests that targeting this signaling may highlight a new therapeutic approach for treatment of CRC.

Targeting CXCR7 improves the efficacy of breast cancer patients with tamoxifen therapy

Monoubiquitination Is Critical for Ovarian Tumor Domain-containing Ubiquitin Aldehyde Binding Protein 1 (Otub1) to Suppress UbcH5 Enzyme and Stabilize p53 Protein*

It is reported that Otub1 is monoubiquitinated by UbcH5 in cells and in vitro, primarily at the lysine 59 and 109 residues, suggesting that this binding interferes with the self-assembly of Ub-charged Ubc H5 (UbcH5∼Ub) conjugates, which is critical for Ub transfer.

FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1

It is demonstrated that the deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1) is a substrate for hydroxylation by FIH on N22, and it is proposed that this results provide new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting Hydroxylases for therapeutic benefit.