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Medline ® Abstract for Reference 33

of 'Principles of cancer immunotherapy'

Ikaros sets thresholds for T cell activation and regulates chromosome propagation.
Avitahl N, Winandy S, Friedrich C, Jones B, Ge Y, Georgopoulos K
Immunity. 1999 Mar;10(3):333-43.
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.
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.