title: The role of Roquin overexpression in the modulation of signaling during in vitro and ex vivo T-cell activation.
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.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, Buk-ku, Daegu, Republic of Korea.
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Ji
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Shin
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Yuh
authors.forename: Ki Beom
authors.initials: KB
authors.lastname: Bae
authors.forename: Seo jin
authors.initials: Sj
authors.lastname: Park
authors.forename: Jun Koo
authors.initials: JK
authors.lastname: Yi
authors.forename: Na Ri
authors.initials: NR
authors.lastname: Kim
authors.forename: Si Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Du Hak
authors.initials: du H
authors.lastname: Yoon
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D008213:Lymphocyte Activation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D048670:MAP Kinase Kinase 4