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Journal of Cell Science, Vol 114, Issue 8 1533-1544, Copyright © 2001 by Company of Biologists


JOURNAL ARTICLES

Mechanism for the transcriptional repression by c-Myc on PDGF (&bgr;)-receptor

H Izumi, C Molander, LZ Penn, A Ishisaki, K Kohno and K Funa
Department of Cell Biology, Institute of Anatomy and Cell Biology, Goteborg University, Box 420, SE-405 30, Gothenburg, Sweden. keiko.funa@anatcell.gu.se

c-Myc plays a key role in the cell cycle dependent control of the PDGF (&bgr;)-receptor mRNA. The mouse platelet-derived growth factor (PDGF) (&bgr;)-receptor promoter contains a CCAAT motif, and NF-Y plays an essential role in its transcription. Coexpression of c-Myc represses PDGF (&bgr;)-receptor luciferase reporter activity, and the CCAAT motif in the promoter is indispensable for this repression. Here we show that c-Myc binds NF-Y subunits, YB and YC, by immunoprecipitation from cotransfected COS-1 cells. The in vitro-translated c-Myc also binds the glutathione S-transferase (GST)-NF-YB fusion protein and GST-NF-YC, but not GST-NF-YA. The most C-terminal region of HAP domains of NF-YB and NF-YC, and the Myc homology boxes, but not the C-terminal bHLHZip domain, are indispensable for the coimmunoprecipitation, and also for the repression of PDGF (&bgr;)-receptor. c-Myc binds NF-Y complex without affecting the efficiency of NF-Y binding to DNA. However, the expression of Myc represses the transcriptional activation of NF-YC when fused to the GAL4 DNA binding domain. Furthermore, this repression was seen only when Myc homology boxes are present, and NF-YC contains the c-Myc binding region.
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