Ikaros induces quiescence and T-cell differentiation in a leukemia cell line.
Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance. It has been hypothesized that Ikaros controls gene expression through its association with chromatin remodeling complexes. The development of leukemia in Ikaros null mice suggests that Ikaros has the characteristics of a tumor suppressor gene. In this report, we show that the introduction of Ikaros into an established mouse Ikaros null T leukemia cell line leads to growth arrest at the G0/G1 stage of the cell cycle. This arrest is associated with up-regulation of the cell cycle-dependent kinase inhibitor p27kip1, the induction of expression of T-cell differentiation markers, and a global and specific increase in histone H3 acetylation status. These studies provide strong evidence that Ikaros possesses the properties of a bona fide tumor suppressor gene for the T-cell lineage and offer insight into the mechanism of Ikaros's tumor suppressive activity.
Kathrein
Katie L
KL
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 320 E. Superior St., Morton 6-639, Chicago, IL 60611, USA.
Lorenz
Rachelle
R
Innes
Angela Minniti
AM
Griffiths
Erin
E
Winandy
Susan
S
D000107:Acetylation; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D006657:Histones / Q000378:metabolism; D051740:Ikaros Transcription Factor; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics; D015854:Up-Regulation
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C497238:Zfpn1a1 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051740:Ikaros Transcription Factor