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

P Noy, H Williams, A Sawasdichai, K Gaston, P-S Jayaraman

Research output: Contribution to journalArticle (Academic Journal)peer-review

27 Citations (Scopus)

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.
Translated title of the contributionPRH/Hex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling
Original languageEnglish
Pages (from-to)2120 - 2134
Number of pages15
JournalMolecular and Cellular Biology
Volume30 (9)
DOIs
Publication statusPublished - May 2010

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