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CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding

Soufi, Abdenour and Noy, Peter and Buckle, Malcolm and Sawasdichai, Anyaporn and Gaston, Kevin and Jayaraman, Padma-Sheela (2009) CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding. Nucleic Acids Research, 37 (2). pp. 3288-3300. ISSN 0305-1048

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URL of Published Version: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19324893

Identification Number/DOI: 10.1093/nar/gkp197

The proline-rich homeodomain protein (PRH/Hex) regulates transcription by binding to specific DNA sequences and regulates mRNA transport by binding to translation initiation factor eIF4E. Protein kinase CK2 plays multiple roles in the regulation of gene expression and cell proliferation. Here, we show that PRH interacts with the β subunit of CK2 in vitro and in cells and that CK2 phosphorylates PRH. Phosphorylation of PRH by CK2 inhibits the DNA binding activity of this protein and dephosphorylation restores DNA binding indicating that this modification acts as a reversible switch. We show that phosphorylation of the homeodomain is sufficient to block DNA binding and we identify two amino acids within this the domain that are phosphorylated by CK2: S163 and S177. Site-directed mutagenesis demonstrates that mutation of either of these residues to glutamic acid partially mimics phosphorylation but is insufficient to completely block DNA binding whereas an S163E/S177E double mutation severely inhibits DNA binding. Significantly, the S163E and S177E mutations and the S163E/S177E double mutation all inhibit the ability of PRH to regulate transcription in cells. Since these amino acids are conserved between many homeodomain proteins, our results suggest that CK2 may regulate the activity of several homeodomain proteins in this manner.

Type of Work:Article
Date:01 June 2009 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Medicine
Department:Institute for Biomedical Research
Subjects:R Medicine (General)
Institution:University of Birmingham
Copyright Holders:Oxford University Press
ID Code:258
Refereed:YES
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