JUPITER, FL, April 10, 2010 For years, scientists have thought of DNA as a passive blueprint capable only of producing specific proteins through RNA transcription. Now, research led by scientists from the Florida campus of The Scripps Research Institute has shown DNA can also act to fine-tune the activity of certain proteins known as nuclear receptors.
These new findings may make it possible to design therapies that could activate specific genes in a highly targeted manner in a number of important diseases including osteoporosis, obesity, autoimmune disease, and cancer.
The study was published April 10, 2011, in the journal Nature Structural & Molecular Biology.
"This study offers the first direct evidence of what we now recognize as critically important interactions," said team leader Patrick R. Griffin, PhD, chair of the Department of Molecular Therapeutics and director of the Translational Research Institute at Scripps Florida. "This new understanding could lead to the development of ways to promote highly targeted activity, which is exactly what you need in order to produce safe and effective therapies."
The new study focuses on the interactions between a protein complex comprising the vitamin D receptor and the retinoic X receptor and their ligands, vitamin D and 9-cis-retinoic acid (a metabolite of vitamin A), respectively, as well as DNA, and a coregulatory protein. Receptors are proteins to which one or more specific kinds of signaling molecules bind.
Scientists at Eli Lilly and Company collaborated on this study to better understand how vitamin D works at its most basic level, given that vitamin D plays a major role in bone health and is thus linked to the company's research platform in osteoporosis.
"These findings will potentially enable us to design safer medicines that work via the vitamin D pathway to help the osteoporotic patient," said Jeffrey A. Dodge, PhD, senior research fello
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Scripps Research Institute