New method developed to relocate misplaced proteins in cells

Originally pyblished by Stanford University, on September 21, 2024

Cells before and after TRAMs were introduced. TRAMs link a shuttle protein (red), and a target protein (green). Without the TRAM, the target protein resides in the nucleus (left), and upon TRAM treatment, the target protein is pulled into the cytoplasm by the shuttle protein (right). Credit: Steven Banik and Christine Ng

Cells are highly controlled spaces that rely on every protein being in the right place. Many diseases, including cancers and neurodegenerative disorders, are associated with misplaced proteins. In some cancers, for instance, a protein that normally stands watch over DNA replicating in the nucleus is sent far from the DNA it is meant to monitor, allowing cancers to grow.

Steven Banik, assistant professor of chemistry in the School of Humanities and Sciences and institute scholar at Sarafan ChEM-H at Stanford University, and his lab have developed a new method to help force misplaced proteins back to their proper homes within cells. The method involves rewiring the activity of naturally occurring shuttles to help move proteins to different parts of the cell. The team has devised a new class of molecules called "targeted relocalization activating molecules" or TRAMs that convince these natural shuttles to take different cargo—like the proteins that get exported from the nucleus in some cancers—along for the ride. Published in Nature on Sept. 18, this strategy could lead to a therapeutic to correct the protein misplacement associated with diseases, and also to create new functions in cells.

"We are taking proteins that are lost and bringing them back home," said Banik.

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