title: FOXP3 can modulate TAL1 transcriptional activity through interaction with LMO2.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is associated with a differentiation block and self-renewal. The transcription factor Forkhead Box P3 (FOXP3) was recently described to be expressed in a variety of malignancies including T-ALL. Here we show that increased FOXP3 levels negatively correlate with expression of genes regulated by the oncogenic TAL1-complex in human T-ALL patient samples as well as a T-ALL cell line ectopically expressing FOXP3. In these cells, FOXP3 expression results in altered regulation of cell cycle progression and reduced cell viability. Finally, we demonstrate that FOXP3 binds LMO2 in vitro, resulting in decreased interaction between LMO2 and TAL1, providing a molecular mechanism for FOXP3-mediated transcriptional modulation in T-ALL. Collectively, our findings provide initial evidence for a novel role of FOXP3 as a tumor suppressor in T-ALL through modulation of TAL1 transcriptional activity.
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Fleskens
authors.affiliation: Division of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Mokry
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: van der Leun
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Huppelschoten
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: C E G M
authors.initials: CE
authors.lastname: Pals
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Peeters
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Coenen
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: B A
authors.initials: BA
authors.lastname: Cardoso
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: J T
authors.initials: JT
authors.lastname: Barata
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.|Division of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Loosdregt
authors.affiliation: Department of Cell Biology, Centre of Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.|Division of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Coffer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002453:Cell Cycle; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000502:physiology*; D006801:Humans; D060588:LIM Domain Proteins / Q000502:physiology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D051858:Forkhead Transcription Factors; D060588:LIM Domain Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D025521:Tumor Suppressor Proteins; C418974:FOXP3 protein, human; C085117:LMO2 protein, human; C067143:TAL1 protein, human