Ikaros sets thresholds for T cell activation and regulates chromosome propagation

Nicole Avitahl, Susan Winandy, Christof Friedrich, Beverly Jones, Yimin Ge, Katia Georgopoulos

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

T cell activation involves the sustained accumulation of T cell receptor (TCR) and IL-2 receptor (IL-2R) mediated signaling events that promote cell cycle entry and progression. The Ikaros family of nuclear factors regulate this process by providing thresholds overcome by receptor signaling. T cells with reduced levels of Ikaros activity require fewer TCR engagement events for activation, exhibit a greater proliferative response to IL-2, and are less sensitive to inhibitors of TCR and IL-2R signaling. Upon T cell activation, Ikaros proteins localize in a higher-order chromatin structure where they colocalize with components of the DNA replication machinery. Proliferating T cells with reduced Ikaros activity display chromosome abnormalities. We propose that participation of Ikaros in higher-order chromatin structures controls cell cycle transitions and restricts DNA replication.

Original languageEnglish (US)
Pages (from-to)333-343
Number of pages11
JournalImmunity
Volume10
Issue number3
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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