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  • Positive Regulation of Interleukin-2 Expression by a Pseudokinase, Tribbles 1, in Activated T Cells.

Positive Regulation of Interleukin-2 Expression by a Pseudokinase, Tribbles 1, in Activated T Cells.

Biological & pharmaceutical bulletin (2015-08-04)
Chiharu Miyajima, Yuka Itoh, Yasumichi Inoue, Hidetoshi Hayashi
ABSTRACT

Tribbles 1 (TRB1), a member of the Tribbles family, is a pseudokinase that is conserved among species and implicated in various human diseases including leukemia, cardiovascular diseases, and metabolic disorders. However, the role of TRB1 in the immune response is not understood. To evaluate this role, we examined regulation of TRB1 expression and the function of TRB1 in interleukin-2 (IL-2) induction in Jurkat cells, a human acute T cell leukemia cell line. We found that TRB1 was strongly induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin in these cells. IL-2 expression was induced in Jurkat cells activated by PMA and ionomycin; however, knockdown of TRB1 resulted in decreased induction of IL-2. TRB1 null Jurkat cells established using the CRISPR/Cas9 system also showed reduction of IL-2 expression on PMA/ionomycin stimulation. TRB1 knockdown also markedly inhibited IL-2 promoter activation. To determine the mechanism of the stimulatory effect on IL-2 induction, we focused on histone deacetylases (HDACs), and found that HDAC1 preferentially interacts with TRB1. TRB1 suppressed the interaction of HDAC1 with nuclear factor of activated T cells 2 (NFAT2), which is a crucial transcription factor for IL-2 induction. These results indicate that TRB1 is a positive regulator of IL-2 induction in activated T cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phorbol 12-myristate 13-acetate, synthetic, ≥98.0% (TLC)
Sigma-Aldrich
Phorbol 12-myristate 13-acetate, ≥99% (TLC), film or powder
Sigma-Aldrich
PMA, for use in molecular biology applications, ≥99% (HPLC)
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8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
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Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
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7-Amino-1,3-naphthalenedisulfonic acid monopotassium salt monohydrate, BioReagent, suitable for fluorescence, ≥98.0% (T)
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Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
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Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
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Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
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Dimethyl sulfoxide, PCR Reagent
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Dimethyl sulfoxide, for molecular biology
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Dimethyl sulfoxide, anhydrous, ≥99.9%
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Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
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