TFG-1 function in protein secretion and oncogenesis
Author: ["Kristen Witte","Amber L. Schuh","Jan Hegermann","Ali Sarkeshik","Jonathan R. Mayers","Katrin Schwarze","John R. Yates III","Stefan Eimer","Anjon Audhya"]
Publication: Nature Cell Biology
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Abstract
Export of proteins from the endoplasmic reticulum in COPII-coated vesicles occurs at defined sites that contain the scaffolding protein Sec16. We identify TFG-1, a new conserved regulator of protein secretion that interacts directly with SEC-16 and controls the export of cargoes from the endoplasmic reticulum in Caenorhabditis elegans. Hydrodynamic studies indicate that TFG-1 forms hexamers that facilitate the co-assembly of SEC-16 with COPII subunits. Consistent with these findings, TFG-1 depletion leads to a marked decline in both SEC-16 and COPII levels at endoplasmic reticulum exit sites. The sequence encoding the amino terminus of human TFG has been previously identified in chromosome translocation events involving two protein kinases, which created a pair of oncogenes. We propose that fusion of these kinases to TFG relocalizes their activities to endoplasmic reticulum exit sites, where they prematurely phosphorylate substrates during endoplasmic reticulum export. Our findings provide a mechanism by which translocations involving TFG can result in cellular transformation and oncogenesis. TFG-1 is identified as a regulator of COPII coat assembly that interacts with SEC-16 to control protein exit from the endoplasmic reticulum. TFG–kinase fusion proteins have been detected in some cancers and might promote oncogenesis by prematurely phosphorylating target substrates as they exit the endoplasmic reticulum.
Cite this article
Witte, K., Schuh, A., Hegermann, J. et al. TFG-1 function in protein secretion and oncogenesis. Nat Cell Biol 13, 550–558 (2011). https://doi.org/10.1038/ncb2225
