spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 29 April 2008
doi: 10.1242/jcs.021774

Journal of Cell Science 121, 1739-1749 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.021774v1
121/10/1739    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Soh, U. J. K.
Right arrow Articles by Low, B. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Soh, U. J. K.
Right arrow Articles by Low, B. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

BNIP2 extra long inhibits RhoA and cellular transformation by Lbc RhoGEF via its BCH domain

Unice J. K. Soh and Boon Chuan Low*

Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Republic of Singapore

* Author for correspondence (e-mail: dbslowbc{at}nus.edu.sg)

Accepted 13 February 2008

Increased expression of BCH-motif-containing molecule at the C-terminal region 1 (BMCC1) correlates with a favourable prognosis in neuroblastoma, but the underlying mechanism remains unknown. We here isolated BNIPXL (BNIP2 Extra Long) as a single contig of the extended, in-vitro-assembled BMCC1. Here, we show that in addition to homophilic interactions, the BNIP2 and Cdc42GAP homology (BCH) domain of BNIPXL interacts with specific conformers of RhoA and also mediates association with the catalytic DH-PH domains of Lbc, a RhoA-specific guanine nucleotide exchange factor (RhoGEF). BNIPXL does not recognize the constitutive active G14V and Q63L mutants of RhoA but targets the fast-cycling F30L and the dominant-negative T19N mutants. A second region at the N-terminus of BNIPXL also targets the proline-rich region of Lbc. Whereas overexpression of BNIPXL reduces active RhoA levels, knockdown of BNIPXL expression has the reverse effect. Consequently, BNIPXL inhibits Lbc-induced oncogenic transformation. Interestingly, BNIPXL can also interact with RhoC, but not with RhoB. Given the importance of RhoA and RhoGEF signaling in tumorigenesis, BNIPXL could suppress cellular transformation by preventing sustained Rho activation in concert with restricting RhoA and Lbc binding via its BCH domain. This could provide a general mechanism for regulating RhoGEFs and their target GTPases.

Key words: BNIP-2, BCH domain, Rho, RhoGEF, Lbc, Cellular transformation


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




© The Company of Biologists Ltd 2008