Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print December 19, 2007
Mol. Biol. Cell 10.1091/mbc.E07-08-0763

A more recent version of this article appeared on March 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-08-0763v1
19/3/822    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yano, H.
Right arrow Articles by Sabe, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yano, H.
Right arrow Articles by Sabe, H.

Submitted on August 10, 2007
Revised on November 28, 2007
Accepted on December 11, 2007

Fbx8 Makes Arf6 Refractory to Function via Ubiquitination

Hajime Yano,* Itaru Kobayashi,*{dagger} Yasuhito Onodera,* Frédéric Luton,{ddagger} Michel Franco,{ddagger} Yuichi Mazaki,* Shigeru Hashimoto,* Kazuhiro Iwai,{sect} Ze’ev Ronai,|| and Hisataka Sabe*{dagger}

*Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; {dagger}Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; {ddagger}Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6097, 06560 Valbonne, France; {sect}Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; ||Signal Transduction Program, The Burnham Institute, La Jolla, CA 92037

Monitoring Editor: Sandra Schmid

The small GTP-binding protein Arf6 regulates membrane remodeling at cell peripheries, and plays crucial roles in higher orders of cellular functions including tumor invasion. Here we show that Fbx8, an F-box protein bearing the Sec7 domain, mediates ubiquitination of Arf6. This ubiquitination did not appear to be linked to immediate proteasomal degradation of Arf6, while Fbx8 knockdown caused hyperactivation of Arf6. Expression of Fbx8 protein was substantially lost in several breast tumor cell lines, in which Arf6 activity is pivotal for their invasion. Forced expression of Fbx8 in these cells suppressed their Arf6 activities and invasive activities, in which the F-box and Sec7 domains of Fbx8 are required. Together with the possible mechanism as to how Fbx8-mediated ubiquitination interferes with the functions of Arf6, we propose that Fbx8 provides a novel suppressive control of Arf6 activity through noncanonical ubiquitination. Our results indicate that dysfunction of Fbx8 expression may contribute to the invasiveness of some breast cancer cells.

Address correspondence to: Hisataka Sabe (sabe{at}obi.or.jp)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.