Carol MacKintosh and her team pick up major awards at the College of Life Sciences Annual Research Review of the Year
Congratulations to Dr Kumara Dissanayake from Carol MacKintosh's group who was awarded the 2011 Howard Elder Prize for his paper on the transcriptional repressor Capicúa [Dissanayake et al Biochem J. 433, 515-525].
Capicúa (Cap-ee-Coo-a) is Catalan for head-and-tail, so named because mutation of the fruit fly version affects early head and tail development. Kumara discovered that the human Capicúa is a missing link that helps explain why oncogenic Ras–Raf signaling stimulates downstream transcription of ETV1 and other genes that are linked to particularly aggressive forms of prostate cancer, melanoma, oligodendroglioma and gastrointestinal stromal tumours. Specifically, Capicúa represses mRNA expression of the PEA3 Ets transcription factors ETV1, ETV4 and ETV5, and this repression is relieved when Capicúa is phosphorylated by the protein kinases ERK and p90RSK that are activated by Raf. Capicúa then binds to the 14-3-3 family of phosphoprotein-binding proteins, which block its binding to DNA.
Kumara found that experimental depletion of Capicúa rendered melanoma cells resistant to the therapeutic effects of drugs that block signaling upstream of ERK. He therefore predicted that the loss of Capicúa might enhance tumourigenesis, and excitingly, mutations in Capicúa were subsequently discovered to contribute to cases of human oligodendroglioma. In addition to its implications for cancer and cancer therapy, Kumara's study also suggests Capicúa as a nexus that interconnects the signaling networks of growth factor signaling, spinocerebellar ataxias and certain cancers. These findings about Capicúa are the first to emerge from a larger project in which Kumara aims to map the Ras/Raf-regulated 14-3-3-binding phosphoproteome of melanoma comprehensively. Currently, Kumara's paper is one of the five most downloaded papers published in the Biochemical Journal during 2011.
The Howard Elder Prize was endowed 27 years ago by Dr Alison Burt in memory of her father (Dr Howard Elder, a former medical graduate of the University of Dundee). The prize is awarded annually to the PhD student or postdoctoral researcher in the College of Life Sciences, University of Dundee, deemed to have published the most significant paper in an area related to cancer.
Kumara's prize maintains the tradition of Howard Elder Prize awardees in the MRC Protein Phosphorylation Unit, with Craig MacKay winning in 2010, Elton Zeqiraj in 2009, and Xu Huang in 2008.
Carol MacKintosh herself received the Brian Cox Senior Investigator Award for Public Engagement at the same event for her contributions over many years to furthering the public understanding of science. These include her activities in the Dundee and Edinburgh International Science Festivals, The Royal Society of Edinburgh Master Classes and the new Science Café in the village of Tayport where her husband Bob has also played a major role in its success.
It has been quite a year for the MacKintosh laboratory since Shuai Chen, a Postdoc in her lab, was awarded the Sir Tim Hunt Prize in August 2011 for the most significant paper in the field of Cell Biology published by a member of the College of Life Sciences.
Capicúa (Cap-ee-Coo-a) is Catalan for head-and-tail, so named because mutation of the fruit fly version affects early head and tail development. Kumara discovered that the human Capicúa is a missing link that helps explain why oncogenic Ras–Raf signaling stimulates downstream transcription of ETV1 and other genes that are linked to particularly aggressive forms of prostate cancer, melanoma, oligodendroglioma and gastrointestinal stromal tumours. Specifically, Capicúa represses mRNA expression of the PEA3 Ets transcription factors ETV1, ETV4 and ETV5, and this repression is relieved when Capicúa is phosphorylated by the protein kinases ERK and p90RSK that are activated by Raf. Capicúa then binds to the 14-3-3 family of phosphoprotein-binding proteins, which block its binding to DNA.
Kumara found that experimental depletion of Capicúa rendered melanoma cells resistant to the therapeutic effects of drugs that block signaling upstream of ERK. He therefore predicted that the loss of Capicúa might enhance tumourigenesis, and excitingly, mutations in Capicúa were subsequently discovered to contribute to cases of human oligodendroglioma. In addition to its implications for cancer and cancer therapy, Kumara's study also suggests Capicúa as a nexus that interconnects the signaling networks of growth factor signaling, spinocerebellar ataxias and certain cancers. These findings about Capicúa are the first to emerge from a larger project in which Kumara aims to map the Ras/Raf-regulated 14-3-3-binding phosphoproteome of melanoma comprehensively. Currently, Kumara's paper is one of the five most downloaded papers published in the Biochemical Journal during 2011.
The Howard Elder Prize was endowed 27 years ago by Dr Alison Burt in memory of her father (Dr Howard Elder, a former medical graduate of the University of Dundee). The prize is awarded annually to the PhD student or postdoctoral researcher in the College of Life Sciences, University of Dundee, deemed to have published the most significant paper in an area related to cancer.
Kumara's prize maintains the tradition of Howard Elder Prize awardees in the MRC Protein Phosphorylation Unit, with Craig MacKay winning in 2010, Elton Zeqiraj in 2009, and Xu Huang in 2008.
Carol MacKintosh herself received the Brian Cox Senior Investigator Award for Public Engagement at the same event for her contributions over many years to furthering the public understanding of science. These include her activities in the Dundee and Edinburgh International Science Festivals, The Royal Society of Edinburgh Master Classes and the new Science Café in the village of Tayport where her husband Bob has also played a major role in its success.
It has been quite a year for the MacKintosh laboratory since Shuai Chen, a Postdoc in her lab, was awarded the Sir Tim Hunt Prize in August 2011 for the most significant paper in the field of Cell Biology published by a member of the College of Life Sciences.