The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes

Kleijn, Miranda; Proud, Christopher G.

doi:10.1186/1471-2091-3-11

Cited by 17 publications

(4 citation statements)

References 62 publications

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“…Replication of viruses and activation of immune cells leads to enhanced production of newly synthesized proteins and thus to increased protein degradation to maintain protein homeostasis. Indeed, activation of T cells leads to a strong increase in the rate of protein synthesis [76,77]. Using virus-specific T cells it was shown that viral infection in mice led to an accumulation of poly-ubiquitylated proteins in CD8 + T cells, 24 h post infection [62].…”

Section: Immunoproteasomes In Protein Homeostasis Contradictory Resultsmentioning

confidence: 99%

On the Role of the Immunoproteasome in Protein Homeostasis

Basler

Groettrup

2021

Cells

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Numerous cellular processes are controlled by the proteasome, a multicatalytic protease in the cytosol and nucleus of all eukaryotic cells, through regulated protein degradation. The immunoproteasome is a special type of proteasome which is inducible under inflammatory conditions and constitutively expressed in hematopoietic cells. MECL-1 (β2i), LMP2 (β1i), and LMP7 (β5i) are the proteolytically active subunits of the immunoproteasome (IP), which is known to shape the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. Furthermore, the immunoproteasome is involved in T cell expansion and inflammatory diseases. In recent years, targeting the immunoproteasome in cancer, autoimmune diseases, and transplantation proved to be therapeutically effective in preclinical animal models. However, the prime function of standard proteasomes and immunoproteasomes is the control of protein homeostasis in cells. To maintain protein homeostasis in cells, proteasomes remove proteins which are not properly folded, which are damaged by stress conditions such as reactive oxygen species formation, or which have to be degraded on the basis of regular protein turnover. In this review we summarize the latest insights on how the immunoproteasome influences protein homeostasis.

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Section: Immunoproteasomes In Protein Homeostasis Contradictory Resultsmentioning

confidence: 99%

On the Role of the Immunoproteasome in Protein Homeostasis

Basler

Groettrup

2021

Cells

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“…Buffy coats used for the isolation of T cells were prepared from freshly drawn blood from healthy donors and were obtained from the Scottish National Blood Transfusion Service (Edinburgh, UK). Mononuclear leukocytes were isolated as described [11]. T cells were suspended in RPMI 1640 medium supplemented with 10% (v/v) heat‐inactivated foetal calf serum (FCS), 1 mM glutamine, 3 U/ml interleukin‐2 (IL‐2, Sigma), 1 μg/ml phytohaemagglutinin (PHA, Sigma), 100 U/ml penicillin G sodium, 100 μg/ml streptomycin sulphate and 0.25 μg/ml amphotericin B.…”

Section: Methodsmentioning

confidence: 99%

Localisation and regulation of the eIF4E‐binding protein 4E‐BP3

et al. 2002

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The cap-binding protein eIF4E-binding protein 3 (4E-BP3) was identi¢ed some years ago, but its properties have not been investigated in detail. In this report, we investigated the regulation and localisation of 4E-BP3. We show that 4E-BP3 is present in the nucleus as well as in the cytoplasm in primary T cells, HEK293 cells and HeLa cells. 4E-BP3 was associated with eIF4E in both cell compartments. Furthermore, 4E-BP3/eIF4E association in the cytoplasm was regulated by serum or interleukin-2 starvation in the di¡erent cell types. Rapamycin did not a¡ect the association of eIF4E with 4E-BP3 in the cytoplasm or in the nucleus.

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“…These non-canonical functions for eIF3 can aid cell proliferation ( Lee et al, 2015 ), or allow cells to rapidly adapt to stresses such as heat shock ( Meyer et al, 2015 ). In the immune system, T cell activation requires a rapid increase in protein synthesis within the first few hours that also involves eIF3 ( Ahern et al, 1974 ; Kleijn and Proud, 2002 ; Miyamoto et al, 2005 ; Ricciardi et al, 2018 ). However, whether eIF3 serves a general or more specific role in T cell activation is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Activation of eIF3 coincides with the recruitment of subunit eIF3j to eIF3 and translation initiation complexes ( Miyamoto et al, 2005 ). Post-translational modifications are also thought to contribute to the early increase in translation, for example activation of the guanine nucleotide exchange factor eIF2B ( Kleijn and Proud, 2002 ). By contrast, the level of the canonical mRNA cap-binding complex eIF4F–composed of translation initiation factors eIF4E, eIF4G, and eIF4A–increases much later after T cell activation ( Mao et al, 1992 ).…”

Section: Introductionmentioning

confidence: 99%

Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

Silva

Ferguson

Chin

et al. 2021

eLife

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Activation of T cells requires a rapid surge in cellular protein synthesis. However, the role of translation initiation in the early induction of specific genes remains unclear. Here we show human translation initiation factor eIF3 interacts with select immune system related mRNAs including those encoding the T cell receptor (TCR) subunits TCRA and TCRB. Binding of eIF3 to the TCRA and TCRB mRNA 3'-untranslated regions (3'-UTRs) depends on CD28 coreceptor signaling and regulates a burst in TCR translation required for robust T cell activation. Use of the TCRA or TCRB 3'-UTRs to control expression of an anti-CD19 chimeric antigen receptor (CAR) improves the ability of CAR-T cells to kill tumor cells in vitro. These results identify a new mechanism of eIF3-mediated translation control that can aid T cell engineering for immunotherapy applications.

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The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes

Cited by 17 publications

References 62 publications

On the Role of the Immunoproteasome in Protein Homeostasis

On the Role of the Immunoproteasome in Protein Homeostasis

Localisation and regulation of the eIF4E‐binding protein 4E‐BP3

Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

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