Yasemin Sancak
Discovered the Rag GTPases that relay amino-acid signals to mTORC1
PhD/postdoc, Sabatini lab, Whitehead Institute/MIT · Assistant Professor of Pharmacology, University of Washington
Sancak Lab, University of Washington ↗ Bluesky@yasesancak.bsky.social ↗
Portrait: UW Dept. of Pharmacology
Yasemin Sancak trained in David Sabatini's lab, where she identified the Rag GTPases as the long-sought link between amino acids and mTORC1: when nutrients are present, the Rags bind raptor and pull mTORC1 to the surface of the lysosome, its site of activation. She went on to show that the Ragulator complex anchors the Rags there and is itself required for amino-acid signalling.
Sancak also helped characterize PRAS40 as an insulin-regulated inhibitor of mTORC1 and DEPTOR as an mTOR-binding inhibitor overexpressed in some cancers. She now runs her own lab in the Department of Pharmacology at the University of Washington, where her focus has shifted to how mitochondria are regulated by calcium signalling.
The timeline below follows Sancak's mTOR-related discoveries gathered in this Atlas.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2007 | M | PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase SAN2007 Identifies PRAS40 as an insulin-regulated inhibitor of the mTORC1 kinase. |
| 2008 | M | The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 SAN2008 Discovers the Rag GTPases bind raptor and mediate amino-acid signalling to mTORC1. |
| 2009 | M | DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival PET2009 Identified DEPTOR as a built-in brake on BOTH mTOR complexes. The twist: in some multiple myelomas DEPTOR is overexpressed, which by relieving a feedback loop actually keeps pro-survival Akt signaling ON - a neat example of how an 'inhibitor' can be co-opted by cancer. |
| 2010 | M | Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids SAN2010 Shows the Ragulator-Rag complex anchors mTORC1 to the lysosomal surface, required for its activation by amino acids. |
| 2011 | M | mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase ZON2011 Showed amino acid sensing starts INSIDE the lysosome: amino acids accumulate in the lumen and the v-ATPase relays that signal outward ('inside-out') to Ragulator-Rag. A surprising twist on where the cell measures its nutrient status. |