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Volumn 21, Issue 1, 2009, Pages 70-77

Immunity and the regulation of protein synthesis: surprising connections

Author keywords

[No Author keywords available]

Indexed keywords

INITIATION FACTOR 2ALPHA; INITIATION FACTOR 4G; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA;

EID: 64049100954     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2009.03.003     Document Type: Review
Times cited : (17)

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    • Munn D.H., Sharma M.D., Baban B., Harding H.P., Zhang Y., Ron D., and Mellor A.L. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22 (2005) 633-642. This paper demonstrates the central role of the GCN2 stress kinase in sensing tryptophane depletion and arresting T cells in response to IDO. GCN2-knockout T cells were not inhibited by IDO-expressing DCs from tumor-draining lymph nodes. IDO induced profound anergy in responding wild-type T cells, but GCN2-knockout cells were refractory to IDO-induced anergy. GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by IDO. Thus GCN2 and its target eIF2-α are key molecules for tolerance establishment and the subversion of the immune system by tumors.
    • (2005) Immunity , vol.22 , pp. 633-642
    • Munn, D.H.1    Sharma, M.D.2    Baban, B.3    Harding, H.P.4    Zhang, Y.5    Ron, D.6    Mellor, A.L.7
  • 45
    • 34248173331 scopus 로고    scopus 로고
    • Indoleamine 2,3-dioxygenase and tumor-induced tolerance
    • Munn D.H., and Mellor A.L. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest 117 (2007) 1147-1154
    • (2007) J Clin Invest , vol.117 , pp. 1147-1154
    • Munn, D.H.1    Mellor, A.L.2
  • 46
  • 47
    • 33744465772 scopus 로고    scopus 로고
    • Activation of the integrated stress response during T helper cell differentiation
    • After priming via signals through the T-cell receptor, naive T helper cells express cytokine mRNA but do not secrete cytokine protein without additional T cell receptor stimulation. This article demonstrates that primed T cells phosphorylate the eukaryotic initiation factor 2-α and accumulate cytoplasmic granules associated with RNA-binding proteins. Restimulation of the cells resulted in rapid eIF2-α dephosphorylation, ribosomal mRNA loading, and cytokine secretion.
    • Scheu S., Stetson D.B., Reinhardt R.L., Leber J.H., Mohrs M., and Locksley R.M. Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 7 (2006) 644-651. After priming via signals through the T-cell receptor, naive T helper cells express cytokine mRNA but do not secrete cytokine protein without additional T cell receptor stimulation. This article demonstrates that primed T cells phosphorylate the eukaryotic initiation factor 2-α and accumulate cytoplasmic granules associated with RNA-binding proteins. Restimulation of the cells resulted in rapid eIF2-α dephosphorylation, ribosomal mRNA loading, and cytokine secretion.
    • (2006) Nat Immunol , vol.7 , pp. 644-651
    • Scheu, S.1    Stetson, D.B.2    Reinhardt, R.L.3    Leber, J.H.4    Mohrs, M.5    Locksley, R.M.6
  • 48
    • 34250200713 scopus 로고    scopus 로고
    • Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs
    • In this article, the role of eIF2-α phosphorylation in the acquisition of cytotoxic activity of mouse NK cells is demonstrated. Although activated murine NK cells can use the granule exocytosis pathway to kill target cells immediately upon recognition, resting murine NK cells are minimally cytotoxic. It is shown that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation.
    • Fehniger T.A., Cai S.F., Cao X., Bredemeyer A.J., Presti R.M., French A.R., and Ley T.J. Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs. Immunity 26 (2007) 798-811. In this article, the role of eIF2-α phosphorylation in the acquisition of cytotoxic activity of mouse NK cells is demonstrated. Although activated murine NK cells can use the granule exocytosis pathway to kill target cells immediately upon recognition, resting murine NK cells are minimally cytotoxic. It is shown that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation.
    • (2007) Immunity , vol.26 , pp. 798-811
    • Fehniger, T.A.1    Cai, S.F.2    Cao, X.3    Bredemeyer, A.J.4    Presti, R.M.5    French, A.R.6    Ley, T.J.7
  • 49


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