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TFG-1 function in protein secretion and oncogenesis.

Authors :
Witte K
Schuh AL
Hegermann J
Sarkeshik A
Mayers JR
Schwarze K
Yates JR 3rd
Eimer S
Audhya A
Source :
Nature cell biology [Nat Cell Biol] 2011 May; Vol. 13 (5), pp. 550-8. Date of Electronic Publication: 2011 Apr 10.
Publication Year :
2011

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.

Details

Language :
English
ISSN :
1476-4679
Volume :
13
Issue :
5
Database :
MEDLINE
Journal :
Nature cell biology
Publication Type :
Academic Journal
Accession number :
21478858
Full Text :
https://doi.org/10.1038/ncb2225