Skip to main content

Research Repository

See what's under the surface

PRH/Hex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling

Noy, Peter; Williams, hannah; Sawasdichai, Anyaporn; Gaston, Kevin; Jayaraman, Padma-Sheela

Authors

Peter Noy

hannah Williams

Anyaporn Sawasdichai

Kevin Gaston

Padma-Sheela Jayaraman



Abstract

The proline-rich homeodomain protein (PRH) plays multiple roles in the control of gene expression during embryonic development and in the adult. Vascular endothelial growth factor (VEGF) is a mitogen that stimulates cell proliferation and survival via cell surface receptors including VEGFR-1 and VEGFR-2. VEGF signaling is of critical importance in angiogenesis and hematopoiesis and is elevated in many tumors. Here we show that PRH binds directly to the promoter regions of the Vegf, Vegfr-1, and Vegfr-2 genes and that in each case PRH represses transcription. We demonstrate that overexpression or knockdown of PRH directly impinges on the survival of both leukemic and tumor cells and that the modulation of VEGF and VEGF receptor signaling by PRH mediates these effects. Our findings demonstrate that PRH is a key regulator of the VEGF signaling pathway and describe a mechanism whereby PRH plays an important role in tumorigenesis and leukemogenesis.

Journal Article Type Article
Publication Date 2010-05
Journal Molecular and Cellular Biology
Print ISSN 0270-7306
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 30
Issue 9
Pages 2120-2134
APA6 Citation Noy, P., Williams, H., Sawasdichai, A., Gaston, K., & Jayaraman, P. (2010). PRH/Hex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling. Molecular and Cellular Biology, 30(9), 2120-2134. doi:10.1128/MCB.01511-09
DOI https://doi.org/10.1128/MCB.01511-09
Publisher URL https://mcb.asm.org/content/30/9/2120


Downloadable Citations