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RaDAR guides proteins into the nucleus
Date:5/22/2014

May 22, 2014, New York, NY A Ludwig Cancer Research study has identified a novel pathway by which proteins are actively and specifically shuttled into the nucleus of a cell. Published online today in Cell, the finding captures a precise molecular barcode that flags proteins for such import and describes the biochemical interaction that drives this critically important process. The discovery could help illuminate the molecular dysfunction that underpins a broad array of ailments, ranging from autoimmune diseases to cancers.

Although small proteins can diffuse passively through pores built into the nuclear membrane, most nuclear proteins have to be actively driven into the nucleus through specialized pores to ensure that the cell functions normally. Proteins targeted to specific compartments in cells often carry a sequence of amino acids that, like a barcode, tells components of the cell's transport machinery where they should be located in order to perform their biochemical duties.

"Until now, only one nuclear import pathway for active transport has been extensively characterized," says Xin Lu, Ludwig director at the University of Oxford whose laboratory led the study. "It targets proteins that encode what's known as the nuclear localization signal (NLS). Yet about half of the proteins that get into the nucleus do not bear an NLS, and how they get there has long puzzled researchers. Now we have discovered an alternative signal by which proteins devoid of NLS are tagged for nuclear import." The finding will help scientists better understand the roles many hitherto poorly characterized proteins play in cellular life, and identify many others that work within the nucleus on such tasks as gene regulation and expression.

The researchers were led to their discovery while investigating how an important tumor suppressor protein known as ASPP, which Lu's laboratory has been studying for many years, gets into the nucleus. Their experim
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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