The FoxO/Bcl-6/cyclin D2 pathway mediates metabolic and growth factor stimulation of proliferation in Min6 pancreatic beta-cells

Journal of Receptor and Signal Transduction Research
Dominique A Glauser, Werner Schlegel

Abstract

Lack of nutrients and growth factors activates FoxO transcription factors in pancreatic beta-cells, whereas PI3K/Akt-dependent inactivation of FoxO favors proliferation. To address the link between FoxO and cell cycle control, we deprived Min6 cells of serum and glucose which activated FoxO and inhibited proliferation. Concomitantly, expression of the transcriptional repressor Bcl-6 was stimulated, whereas cyclin D2 was lowered. Gain of function approaches indicated that FoxO activation was sufficient to activate bcl-6 transcription, while Bcl-6 repressed cyclin D2 transcription and proliferation. Thus, in pancreatic beta-cells, the FoxO/Bcl6/cyclin D2 pathway connects nutrient and growth factor status to cell cycle control, and may therefore be considered for its therapeutic potential in diabetes.

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Citations

Aug 25, 2012·Nature Reviews. Immunology·Stephen M HedrickErica L Stone
Nov 30, 2016·Molecular Immunology·Markus M XieAlexander L Dent
Sep 24, 2010·Nature Reviews. Molecular Cell Biology·Marisa R Buchakjian, Sally Kornbluth
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May 4, 2018·Oncoimmunology·Beata PyrzynskaMagdalena Winiarska
May 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jeng Yie ChanD Ross Laybutt

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