Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation resulting in increased repression of VEGF signalling genes

Peter Noy, Kevin Gaston, Padma-Sheela Jayaraman

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

6 Citations (Scopus)
230 Downloads (Pure)

Abstract

The PRH/Hhex transcription factor represses multiple genes in the VEGF signalling pathway (VSP) to inhibit myeloid cell survival. Protein kinase CK2 phosphorylates PRH and counteracts the inhibitory effect of this protein on cell survival by blocking the repression of VSP genes. Here we show that the BCR-ABL/Src kinase inhibitor dasatinib decreases PRH phosphorylation and increases PRH-dependent repression of Vegf and Vegfr-1. Moreover in the absence of PRH, dasatinib does not inhibit cell survival as effectively as in PRH expressing cells. Thus the re-establishment of gene control by PRH is in part responsible for the therapeutic effects of dasatinib.
Original languageEnglish
Pages (from-to)1434-1437
Number of pages4
JournalLeukemia Research
Volume36
Issue number11
Early online date5 Aug 2012
DOIs
Publication statusPublished - Nov 2012

Bibliographical note

Date of Acceptance: 16/07/2012

Keywords

  • Leukaemia
  • Phosphorylation
  • BCR-ABL
  • Transcription

Fingerprint Dive into the research topics of 'Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation resulting in increased repression of VEGF signalling genes'. Together they form a unique fingerprint.

Cite this