Phosphorylation of PRH/HHEX by Protein Kinase CK2 regulates cell proliferation and cell migration in diverse cell types

P-S Jayaraman, Kerry Wadey, Sarah George, Kevin Gaston

Research output: Chapter in Book/Report/Conference proceedingChapter in a book

283 Downloads (Pure)

Abstract

Disruption of the regulatory mechanisms that control cell proliferation and cell migration results in multiple disease states including cancer and leukemia. The Proline-Rich Homeodomain protein (PRH)/haematopoietically expressed homeobox protein (HHEX) is a transcription factor that controls cell proliferation and cell migration in a variety of tissues in the adult and in the embryo. Phosphorylation of PRH by Protein Kinase CK2 (Casein Kinase II) stops PRH from binding to DNA and regulating the transcription of its direct target genes. In leukaemic cells phosphorylation also results in the production of a transdominant-negative truncated PRH phosphoprotein by the proteasome. Phosphorylation of PRH is increased in breast and prostate cancer cells and the consequent loss of PRH activity increases cell proliferation and migration. PRH also regulates the proliferation of vascular smooth muscle cells and CK2-dependent phosphorylation of PRH in these cells accompanies increased cell proliferation during intimal thickening. Thus the ability of PRH to regulate cell behaviour and the control of PRH by CK2 is not limited to a specific cell type or tissue. This raises the possibility that the PRH-CK2 axis could be targeted in a variety of disease states ranging from multiple cancers to the intimal thickening that occurs in vein bypass graft failure and restenosis.
Original languageEnglish
Title of host publicationGene expression and regulation in mammalian cells
Subtitle of host publicationtranscription from general aspects
PublisherInTechPublication
Chapter12
Pages237-255
Number of pages19
ISBN (Electronic)9789535138563
ISBN (Print)9789535138556
DOIs
Publication statusPublished - 21 Feb 2018

Fingerprint Dive into the research topics of 'Phosphorylation of PRH/HHEX by Protein Kinase CK2 regulates cell proliferation and cell migration in diverse cell types'. Together they form a unique fingerprint.

  • Cite this

    Jayaraman, P-S., Wadey, K., George, S., & Gaston, K. (2018). Phosphorylation of PRH/HHEX by Protein Kinase CK2 regulates cell proliferation and cell migration in diverse cell types. In Gene expression and regulation in mammalian cells: transcription from general aspects (pp. 237-255). InTechPublication. https://doi.org/10.5772/intechopen.70352