ArticleNucleic acids research2012
Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Article
- The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.Journal of translational medicine · 2024Article
- The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease.Frontiers in immunology · 2023Review
- CK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis.Nature communications · 2022Article
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.Exploration of targeted anti-tumor therapy · 2021Review
- A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation.Nature communications · 2020Article
- Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX.Oncogenesis · 2020Article
- Deciphering the scalene association among type-2 diabetes mellitus, prostate cancer, and chronic myeloid leukemia via enrichment analysis of disease-gene network.Cancer medicine · 2019Article
- Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism.Vascular pharmacology · 2017Article
- Proline-Rich Homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth.Oncogenesis · 2017Article
- CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation.Oncogenesis · 2017Article
- Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion.Cell & bioscience · 2016Review
- Hhex Is Necessary for the Hepatic Differentiation of Mouse ES Cells and Acts via Vegf Signaling.PloS one · 2016Article
- Protein kinase CK2 in breast cancer: the CK2β regulatory subunit takes center stage in epithelial plasticity.Cellular and molecular life sciences : CMLS · 2015Review
- PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin.Oncogene · 2014Article
- Aurora B and Kif2A control microtubule length for assembly of a functional central spindle during anaphase.The Journal of cell biology · 2013Article
- Regulation of a truncated isoform of AMP-activated protein kinase α (AMPKα) in response to hypoxia in the muscle of Pacific oyster Crassostrea gigas.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Protein kinase CK2 promotes cell survival and the activity of this kinase is elevated in several cancers including chronic myeloid leukaemia. We have shown previously that phosphorylation of the Proline-Rich Homeodomain protein (PRH/Hhex) by CK2 inhibits the DNA-binding activity of this transcription factor. Furthermore, PRH represses the transcription of multiple genes encoding components of the VEGF-signalling pathway and thereby influences cell survival. Here we show that the inhibitory effects of PRH on cell proliferation are abrogated by CK2 and that CK2 inhibits the binding of PRH at the Vegfr-1 promoter. Phosphorylation of PRH by CK2 also decreases the nuclear association of PRH and induces its cleavage by the proteasome. Moreover, cleavage of phosphorylated PRH produces a stable truncated cleavage product which we have termed PRHΔC (HhexΔC). PRHΔC acts as a transdominant negative regulator of full-length PRH by sequestering TLE proteins that function as PRH co-repressors. We show that this novel regulatory mechanism results in the alleviation of PRH-mediated repression of Vegfr-1. We suggest that the re-establishment of PRH function through inhibition of CK2 could be of value in treatment of myeloid leukaemias, as well as other tumour types in which PRH is inactivated by phosphorylation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.