Research Repository

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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), doi:10.3390/cancers10090283. ISSN 2072-6694

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

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., Gaston, K., & George, S. (2017). Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism. Vascular Pharmacology, 99, (34--44). doi:10.1016/j.vph.2017.09.004. ISSN 1537-1891

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

Proline-rich homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth (2017)
Journal Article
Kershaw, R., Roberts, D., Wragg, J., Shaaban, A., Humphreys, E., Halsall, J., …-S. Jayaraman, P. (2017). Proline-rich homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth. Oncogenesis, 6(6), doi:10.1038/oncsis.2017.42. ISSN 2157-9024

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

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. (2017). Proline-rich homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth. Oncogenesis, 6, doi: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

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., Wadey, K. S., & Jayaraman, P. (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, doi: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

Novel mechanisms of resistance to vemurafenib in melanoma – V600E B-Raf reversion and switching VEGF-A splice isoform expression (2015)
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

PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin (2013)
Journal Article
Kershaw, R. M., Hasan Siddiqui, Y., Roberts, D., Jayaraman, P., & Gaston, K. (2013). PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Oncogene, 33(49), doi:10.1038/onc.2013.496. ISSN 0950-9232

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

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., & Gaston, K. (2014). PRH/Hhex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Oncogene, 33, 5592--5600. doi: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

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. (2012). Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation resulting in increased repression of VEGF signalling genes. Leukemia Research, 36, 1434--1437. doi: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

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. doi: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

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), doi: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

The regulation of human papillomavirus gene expression by the E2 protein: keeping a finger in every pie (2012)
Book
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. Wymondham: 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

Protein flexibility directs DNA recognition by the papillomavirus E2 proteins (2010)
Journal Article
Brown, C. A., Campos-León, K., Strickland, M., Williams, C., Fairweather, V., Brady, R. L., …Gaston, K. (2011). Protein flexibility directs DNA recognition by the papillomavirus E2 proteins. Nucleic Acids Research, 39(7), 2969--2980. doi:10.1093/nar/gkq1217

Although DNA flexibility is known to play an important role in DNA–protein interactions, the importance of protein flexibility is less well understood. Here, we show that protein dynamics are important in DNA recognition using the well-characterized... Read More

DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers (2010)
Journal Article
Soufi, A., Sawasdichai, A., Shukla, A., Noy, P., Dafforn, T., Smith, C., …Gaston, K. (2010). DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers. Nucleic Acids Research, 38(21), 7513--7525. doi:10.1093/nar/gkq659

Protein self-organization is essential for the establishment and maintenance of nuclear architecture and for the regulation of gene expression. We have shown previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to form oligom... Read More

In situ subcellular fractionation of adherent and non-adherent mammalian cells (2010)
Journal Article
Sawasdichai, A., Chen, H., Abdul Hamid, N., Jayaraman, P., & Gaston, K. (2010). In situ subcellular fractionation of adherent and non-adherent mammalian cells. Journal of Visualized Experiments, 41, doi:10.3791/1958

Protein function is intimately coupled to protein localization. Although some proteins are restricted to a specific location or subcellular compartment, many proteins are present as a freely diffusing population in free exchange with a sub-population... Read More