New study creates first 3-D vision of cancer target

27-Jan-2016 - United Kingdom

A team from the University of Leicester has for the first time published a detailed description of a protein linked to many types of cancer.

The lab-based study from the Department of Molecular and Cell Biology now provides an opportunity for scientists to develop drugs to target this protein.

Dr Cyril Dominguez who led the work at Leicester said: "My research field is structural biology. The proteins that we have studied, called Sam68 and T-STAR, are very similar and overexpression of Sam68 has been shown to correlate with poor prognosis in many types of cancers.

"Our results provide atomic resolution details on how Sam68 binds specifically to its RNA target. Furthermore, we show that Sam68 forms a homodimer that has never been described before and is crucial for its function in RNA splicing.

"This is important because this basic research set the grounds for structure-based drug design approaches. If we can identify or design drugs that bind specifically at the dimerization interface, we will be able to prevent the function of these proteins in cells, which could have implications for novel cancer treatments.

"Now that we have a high-resolution structure of Sam68 and T-STAR and a high-throughput binding assay, we are in discussion to collaborate with a major drug discovery consortium to screen a very large library of compounds to inhibit the function of Sam68."

Original publication

Mikael Feracci, Jaelle N. Foot, Sushma N. Grellscheid, Marina Danilenko, Ralf Stehle, Oksana Gonchar, Hyun-Seo Kang, Caroline Dalgliesh, N. Helge Meyer, Yilei Liu, Albert Lahat, Michael Sattler, Ian C. Eperon, David J. Elliott & Cyril Dominguez; "Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68"; Nature Comm.; 2016

https://www.bionity.com/en/news/156538/new-study-creates-first-3-d-vision-of-cancer-target.html