FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf.

FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf. Research Abstract Details 

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FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf. Abstract Text:

Caroline Bouchard,Soyoung Lee,Viola Paulus-Hock,Christoph Loddenkemper,Martin Eilers,Clemens A Schmitt,Caroline Bouchard,Soyoung Lee,Viola Paulus-Hock,Christoph Loddenkemper,Martin Eilers,Clemens A Schmitt,

FoxO transcription factors play critical roles in cell cycle control and cellular stress responses, and abrogation of FoxO function promotes focus formation by Myc in vitro. Here we show that stable introduction of a dominant-negative FoxO moiety (dnFoxO) into Emu-myc transgenic hematopoietic stem cells accelerates lymphoma development in recipient mice by attenuating Myc-induced apoptosis. When expressed in Emu-myc; p53(+/-) progenitor cells, dnFoxO alleviates the pressure to inactivate the remaining p53 allele in upcoming lymphomas. Expression of the p53 upstream regulator p19(Arf) is virtually undetectable in most dnFoxO-positive Myc-driven lymphomas. We find that FoxO proteins bind to a distinct site within the Ink4a/Arf locus and activate Arf expression. Moreover, constitutive Myc signaling induces a marked increase in nuclear FoxO levels and stimulates binding of FoxO proteins to the Arf locus. These data demonstrate that FoxO factors mediate Myc-induced Arf expression and provide direct genetic evidence for their tumor-suppressive capacity.

FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf. Publishing Authors By Initials

C Bouchard,S Lee,V Paulus-Hock,C Loddenkemper,M Eilers,CA Schmitt,C Bouchard,S Lee,V Paulus-Hock,C Loddenkemper,M Eilers,CA Schmitt,

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FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Genes & development

VOLUME: 21

Page Numbers: 2775-87

Journal Abbreviation: Genes Dev.

ISSN: 0890-9369

DAY: 1

MONTH: Nov

YEAR: 2007

FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf. Information

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LANGUAGE: eng

NlmUniqueID: 8711660

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Grant and Affiliation Information for FoxO transcription factors suppress Myc-driven lymphomagenesis via direct activation of Arf.

AFFILIATION: Institute of Molecular Biology and Tumor Research, 35033 Marburg, Germany.

Country: United States

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MEDLINETA: Genes Dev

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