Ikaros sets thresholds for T cell activation and regulates chromosome propagation.
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.
Avitahl
N
N
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
Winandy
S
S
Friedrich
C
C
Jones
B
B
Ge
Y
Y
Georgopoulos
K
K
D000818:Animals; D002453:Cell Cycle / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations / Q000276:immunology; D002875:Chromosomes / Q000502:physiology*; D004268:DNA-Binding Proteins; D051740:Ikaros Transcription Factor; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009154:Mutation / Q000276:immunology; D016196:S Phase / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor