title: TFG-1 function in protein secretion and oncogenesis.
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.
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin-Madison Medical School, 1300 University Avenue, Madison, Wisconsin 53706, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Witte
authors.forename: Amber L
authors.initials: AL
authors.lastname: Schuh
authors.forename: Jan
authors.initials: J
authors.lastname: Hegermann
authors.forename: Ali
authors.initials: A
authors.lastname: Sarkeshik
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Mayers
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarze
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Stefan
authors.initials: S
authors.lastname: Eimer
authors.forename: Anjon
authors.initials: A
authors.lastname: Audhya
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; C484337:dnj-29 protein, C elegans; D008565:Membrane Proteins