TFG-1 function in protein secretion and oncogenesis

Nat Cell Biol. 2011 May;13(5):550-8. doi: 10.1038/ncb2225. Epub 2011 Apr 10.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology
  • Cell Transformation, Neoplastic*
  • Endoplasmic Reticulum / metabolism
  • Humans

Substances

  • Caenorhabditis elegans Proteins
  • dnj-29 protein, C elegans