Format

Send to

Choose Destination
FEBS Lett. 2010 Jul 2;584(13):2909-15. doi: 10.1016/j.febslet.2010.05.009. Epub 2010 May 13.

Human ROBO1 is cleaved by metalloproteinases and gamma-secretase and migrates to the nucleus in cancer cells.

Author information

1
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.

Abstract

ROBO1 is a receptor mediating Slit-induced repulsive action on axon guidance and differentially expressed in human cancers. Although ROBO1 ectodomain has been detected, the cleavage site had not been determined. In this study we identified the precise cleavage site of ROBO1. We also report multi-step proteolysis of ROBO1 by metalloproteinases and gamma-secretase, producing two carboxy-terminal fragments, ROBO1-CTF1 at 129-kDa and ROBO1-CTF2 at 118-kDa. We have further demonstrated nuclear accumulation of ROBO1, which is abolished by either a metalloproteinase inhibitor TAPI-1 or a gamma-secretase inhibitor L-685,458. ROBO1 may function beyond the receptor through stepwise cleavages and translocation to the nucleus.

PMID:
20471383
DOI:
10.1016/j.febslet.2010.05.009
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center