RGC-32 is a novel regulator of the T-lymphocyte cell cycle

Cosmin A. Tegla, Cornelia D. Cudrici, Vinh Nguyen, Jacob Danoff, Adam M. Kruszewski, Dallas Boodhoo, Armugam P. Mekala, Sonia I. Vlaicu, Ching Chen, Violeta Rus, Tudor C. Badea, Horea Rus*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We have previously shown that RGC-32 is involved in cell cycle regulation in vitro. To define the in vivo role of RGC-32, we generated RGC-32 knockout mice. These mice developed normally and did not spontaneously develop overt tumors. To assess the effect of RGC-32 deficiency on cell cycle activation in T cells, we determined the proliferative rates of CD4+ and CD8+ T cells from the spleens of RGC-32-/- mice, as compared to wild-type (WT, RGC-32+/+) control mice. After stimulation with anti-CD3/anti-CD28, CD4+ T cells from RGC-32-/- mice displayed a significant increase in [3H]-thymidine incorporation when compared to WT mice. In addition, both CD4+ and CD8+ T cells from RGC-32-/- mice displayed a significant increase in the proportion of proliferating Ki67+ cells, indicating that in T cells, RGC-32 has an inhibitory effect on cell cycle activation induced by T-cell receptor/CD28 engagement. Furthermore, Akt and FOXO1 phosphorylation induced in stimulated CD4+ T-cells from RGC-32-/- mice were significantly higher, indicating that RGC-32 inhibits cell cycle activation by suppressing FOXO1 activation. We also found that IL-2 mRNA and protein expression were significantly increased in RGC-32-/- CD4+ T cells when compared to RGC-32+/+ CD4+ T cells. In addition, the effect of RGC-32 on the cell cycle and IL-2 expression was inhibited by pretreatment of the samples with LY294002, indicating a role for phosphatidylinositol 3-kinase (PI3K). Thus, RGC-32 is involved in controlling the cell cycle of T cells in vivo, and this effect is mediated by IL-2 in a PI3K-dependent fashion.

Original languageEnglish (US)
Pages (from-to)328-337
Number of pages10
JournalExperimental and Molecular Pathology
Volume98
Issue number3
DOIs
StatePublished - Jun 1 2015

Keywords

  • Akt
  • Cell cycle
  • IL-2
  • Knockout mouse
  • RGC-32
  • T-cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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  • Cite this

    Tegla, C. A., Cudrici, C. D., Nguyen, V., Danoff, J., Kruszewski, A. M., Boodhoo, D., Mekala, A. P., Vlaicu, S. I., Chen, C., Rus, V., Badea, T. C., & Rus, H. (2015). RGC-32 is a novel regulator of the T-lymphocyte cell cycle. Experimental and Molecular Pathology, 98(3), 328-337. https://doi.org/10.1016/j.yexmp.2015.03.011