The role of Roquin overexpression in the modulation of signaling during in vitro and ex vivo T-cell activation

Hei Jung Kim, Young Rae Ji, Myoung Ok Kim, Dong Hoon Yu, Mi Jung Shin, Hyung Soo Yuh, Ki Beom Bae, Seo jin Park, Jun Koo Yi, Na Ri Kim, Si Jun Park, Du Hak Yoon, Won Ha Lee, Sanggyu Lee, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The T-cell receptor (TCR) engages with an antigen and initiates a signaling cascade that leads to the activation of transcription factors. Roquin, a protein encoded by the RC3H1 gene and characterized as an immune regulator, was recently identified as a novel RING-type ubiquitin ligase family member, but the mechanisms by which Roquin regulates T-cell responses are unclear. We used the EL-4 murine lymphoma cell line to elucidate the role of Roquin in vitro. Roquin-overexpressing EL-4 cells became hyper-responsive after anti-CD3/CD28 stimulation in vitro and were a major source of the cytokines IL-2 and TNF-α. Upon activation, these cells showed particularly enhanced production of IL-2 and TNF-α. To clarify the important role played by Roquin in T-cell responses ex vivo, we generated T-cell-specific Roquin transgenic (Tg) mice. Roquin-Tg CD4 + T-cells showed enhanced production of IL-2 and TNF-α in response to TCR stimulation with anti-CD28 co-stimulation. Further studies are necessary to investigate the role of Roquin in the regulation of primary T-cell activation, survival, and differentiation.

Original languageEnglish (US)
Pages (from-to)280-286
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume417
Issue number1
DOIs
StatePublished - Jan 6 2012

Bibliographical note

Funding Information:
This study was supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and was funded by the Ministry of Education, Science and Technology ( 2010-0028076 ), a grant from the Korean Ministry of Education, Science and Technology (The Regional Core Research Program) , a grant from the Next-Generation BioGreen 21 Program (No. PJ008050), and the SRC program of Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government ( 2009-0063409 ).

Keywords

  • Roquin
  • T-cell activation
  • Transgenic mice

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