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Biomolecular Condensation of the Human Papillomavirus E2 Master Regulator with p53: Implications in Viral Replication (2022)
Journal Article
Susana Borkosky, S., Fassolari, M., Campos-León, K., Hugo Rossi, A., Salgueiro, M., Antonela Pascuale, C., …de Prat Gay, G. (2022). Biomolecular Condensation of the Human Papillomavirus E2 Master Regulator with p53: Implications in Viral Replication. Journal of Molecular Biology, Article 167889. https://doi.org/10.1016/j.jmb.2022.167889

p53 exerts its tumour suppressor activity by modulating hundreds of genes and it can also repress viral replication. Such is the case of human papillomavirus (HPV) through targeting the E2 master regulator, but the biochemical mechanism is not known.... Read More about Biomolecular Condensation of the Human Papillomavirus E2 Master Regulator with p53: Implications in Viral Replication.

Targeting protein kinase CK2 in the treatment of cholangiocarcinoma (2021)
Journal Article
Jayaraman, P. S., & Gaston, K. (2021). Targeting protein kinase CK2 in the treatment of cholangiocarcinoma. Exploration of Targeted Anti-tumor Therapy, 2(5), 434-447. https://doi.org/10.37349/etat.2021.00055

Cholangiocarcinoma (CCA) is a disease with a very poor prognosis and limited treatment options. Although targeted therapies directed towards specific mutations found in CCA are becoming available and are showing great potential, many tumors do not ca... Read More about Targeting protein kinase CK2 in the treatment of cholangiocarcinoma.

Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX (2020)
Journal Article
Marcolino De Assis, E., Siddiqui, Y. H., van den Bosch, M., Poole, A. W., Jayaraman, P., & Gaston, K. (2020). Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX. Oncogenesis, 9, Article 10. https://doi.org/10.1038/s41389-020-0189-0

Cancer cells go through a process known as epithelial–mesenchymal transition (EMT) during which they acquire the ability to migrate and invade extracellular matrix. Some cells also acquire the ability to move across a layer of endothelial cells to en... Read More about Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX.

A runaway PRH/HHEX-Notch3 positive feedback loop drives cholangiocarcinoma and determines response to CDK4/6 inhibition (2019)
Journal Article
Jayaraman, P.-S., Kitchen, P., Gaston, K., Lee, K. Y., Afford, S., Clark, D., …Sawasdichai, A. (2020). A runaway PRH/HHEX-Notch3 positive feedback loop drives cholangiocarcinoma and determines response to CDK4/6 inhibition. Cancer Research, 80(4), 757-770. https://doi.org/10.1158/0008-5472.can-19-0942

Aberrant Notch and Wnt signalling are known drivers of cholangiocarcinoma (CCA) but the underlying factors that initiate and maintain these pathways are not known. Here we show that the PRH/HHEX transcription factor forms a positive transcriptional f... Read More about A runaway PRH/HHEX-Notch3 positive feedback loop drives cholangiocarcinoma and determines response to CDK4/6 inhibition.

Signaling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance (2019)
Journal Article
Fouassier, L., Marzioni, M., Afonso, M. B., Dooley, S., Gaston, K., Giannelli, G., …Coulouarn, C. (2019). Signaling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance. Liver International, 39(S1), 43-62. https://doi.org/10.1111/liv.14102

Cholangiocarcinoma (CCA) is a deadly disease. While surgery may attain cure in a minor fraction of cases, therapeutic options in either the adjuvant or advanced setting are limited. The possibility of advancing the efficacy of therapeutic approaches... Read More about Signaling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance.

CX-4945 induces methuosis in cholangiocarcinoma cell lines by a CK2-independent mechanism (2018)
Journal Article
Lertsuwan, J., Lertsuwan, K., Sawasdichai, A., Tasnawijitwong, N., Lee, K., Kitchen, P., …Satayavivad, J. (2018). CX-4945 induces methuosis in cholangiocarcinoma cell lines by a CK2-independent mechanism. Cancers, 10(9), Article 283. https://doi.org/10.3390/cancers10090283

Cholangiocarcinoma is a disease with a poor prognosis and increasing incidence and hence there is a pressing unmet clinical need for new adjuvant treatments. Protein kinase CK2 (previously casein kinase II) is a ubiquitously expressed protein kinase... Read More about CX-4945 induces methuosis in cholangiocarcinoma cell lines by a CK2-independent mechanism.

Phosphorylation of PRH/HHEX by Protein Kinase CK2 regulates cell proliferation and cell migration in diverse cell types (2018)
Book Chapter
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 F. Uchiumi (Ed.), Gene expression and regulation in mammalian cells (237--255). InTech. https://doi.org/10.5772/intechopen.72902

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 (HHE... Read More about Phosphorylation of PRH/HHEX by Protein Kinase CK2 regulates cell proliferation and cell migration in diverse cell types.

Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism (2017)
Journal Article
Wadey, K., Brown, B., Sala-Newby, G., Jayaraman, P.-S., Gaston, K., & George, S. (2017). Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism. Vascular Pharmacology, 99, 34--44. https://doi.org/10.1016/j.vph.2017.09.004

Neointimal hyperplasia is a product of VSMC replication and consequent accumulation within the blood vessel wall. In this study, we determined whether inhibition of protein kinase CK2 and the resultant stabilisation of proline-rich homeodomain (PRH)... Read More about Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism.

The enigmatic origin of papillomavirus protein domains (2017)
Journal Article
Puustusmaa, M., Kirsip, H., Gaston, K., & Abroi, A. (2017). The enigmatic origin of papillomavirus protein domains. Viruses, 9(9), Article 240. https://doi.org/10.3390/v9090240

Almost a century has passed since the discovery of papillomaviruses. A few decades of research have given a wealth of information on the molecular biology of papillomaviruses. Several excellent studies have been performed looking at the long- and sho... Read More about The enigmatic origin of papillomavirus protein domains.

Proline-rich homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth (2017)
Journal Article
Kershaw, R. M., Roberts, D., Wragg, J., Shaaban, A. M., Humphreys, E., Halsall, J., …Jayaraman, P.-S. (2017). Proline-rich homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth. Oncogenesis, 6(6), Article e346. https://doi.org/10.1038/oncsis.2017.42

Breast tumours progress from hyperplasia to ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). PRH/HHEX (Proline Rich Homeodomain/Haematopoietically expressed homeobox) is a transcription factor that displays both tumour suppressor... Read More about Proline-rich homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth.

Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion (2016)
Journal Article
Gaston, K., Tsitsilianos, M.-A., Wadey, K. S., & Jayaraman, P.-S. (2016). Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion. Cell and Bioscience, 6, Article 12. https://doi.org/10.1186/s13578-016-0077-7

The Proline Rich Homeodomain protein (PRH), also known as Haematopoietically Expressed homeobox (HHEX), is an essential transcription factor in embryonic development and in the adult. The PRH protein forms oligomeric complexes that bind to tandemly r... Read More about Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion.

Novel mechanisms of resistance to vemurafenib in melanoma – V600E B-Raf reversion and switching VEGF-A splice isoform expression (2014)
Journal Article
Beazley Long, N., Gaston, K., Harper, S. J., Orlando, A., & Bates, D. O. (2015). Novel mechanisms of resistance to vemurafenib in melanoma – V600E B-Raf reversion and switching VEGF-A splice isoform expression. American Journal of Cancer Research, 5(1), 433--441

Targeting activating mutations in the proto-oncogene B-Raf, in melanoma, has led to increases in progression free survival. Treatment with vemurafenib, which inhibits the most common activating-mutated form of B-Raf (B-RafV600E), eventually results i... Read More about Novel mechanisms of resistance to vemurafenib in melanoma – V600E B-Raf reversion and switching VEGF-A splice isoform expression.

Proline Rich Homeodomain (PRH/HHEX) protein in the control of haematopoiesis and myeloid cell proliferation and its potential as a therapeutic target in myeloid leukaemias and other cancers. (2013)
Book Chapter
Kershaw, R., Gaston, K., & Jayaraman, P. (2013). Proline Rich Homeodomain (PRH/HHEX) protein in the control of haematopoiesis and myeloid cell proliferation and its potential as a therapeutic target in myeloid leukaemias and other cancers. In S. Douglas (Ed.), Myeloid cells: biology & regulation, role in cancer progression and potential implications for therapyNOVA Publishers

PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin (2013)
Journal Article
Kershaw, R. M., Siddiqui, Y. H., Roberts, D., Jayaraman, P.-S., & Gaston, K. (2014). PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Oncogene, 33, 5592-5600. https://doi.org/10.1038/onc.2013.496

PRH/HHex (proline-rich homeodomain protein) is a transcription factor that controls cell proliferation and cell differentiation in a variety of tissues. Aberrant subcellular localisation of PRH is associated with breast cancer and thyroid cancer. Fur... Read More about PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin.

Small DNA tumour viruses (2012)
Book
(2012). K. Gaston (Ed.), Small DNA tumour viruses. Wymondham: Caister Academic Press

The regulation of human papillomavirus gene expression by the E2 protein: keeping a finger in every pie (2012)
Book Chapter
Graham, S. V., & Gaston, K. L. (2012). The regulation of human papillomavirus gene expression by the E2 protein: keeping a finger in every pie. In K. Gaston (Ed.), Small DNA tumour viruses, 37--53. Caister Academic Press

The human papillomavirus (HPV) genome is around 8000 base pairs in length and it encodes only eight proteins, a limited number of protein isoforms and no known microRNAs. Despite this relative paucity of genes and gene products these viruses are high... Read More about The regulation of human papillomavirus gene expression by the E2 protein: keeping a finger in every pie.

Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation resulting in increased repression of VEGF signalling genes (2012)
Journal Article
Noy, P., Gaston, K., & Jayaraman, P.-S. (2012). Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation resulting in increased repression of VEGF signalling genes. Leukemia Research, 36(11), 1434-1437. https://doi.org/10.1016/j.leukres.2012.07.013

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

Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival (2012)
Journal Article
Noy, P., Sawasdichai, A., Jayaraman, P., & Gaston, K. (2012). Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival. Nucleic Acids Research, 40(18), 9008--9020. https://doi.org/10.1093/nar/gks687

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 inhi... Read More about Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival.

The proline rich homeodomain protein PRH/Hhex forms stable oligomers that are highly resistant to denaturation (2012)
Journal Article
Shukla, A., Burton, N. M., Jayaraman, P., & Gaston, K. (2012). The proline rich homeodomain protein PRH/Hhex forms stable oligomers that are highly resistant to denaturation. PLoS ONE, 7(4), Article e35984. https://doi.org/10.1371/journal.pone.0035984

Background: Many transcription factors control gene expression by binding to specific DNA sequences at or near the genes that they regulate. However, some transcription factors play more global roles in the control of gene expression by altering the... Read More about The proline rich homeodomain protein PRH/Hhex forms stable oligomers that are highly resistant to denaturation.