JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1083/jcb.200812060
The Journal of Cell Biology, Vol. 185, No. 6, 949-957
The Rockefeller University Press, 0021-9525 $30.00
© Lee et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3156K)
Right arrow PDF+supp data (4497K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material
Right arrow Alert me when this article is cited
Right arrow View original image data
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Lee, J.-L.
Right arrow Articles by Chen, J.-Y.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J.-L.
Right arrow Articles by Chen, J.-Y.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Report

Acetylation and activation of STAT3 mediated by nuclear translocation of CD44



Jia-Lin Lee1, Mei-Jung Wang1, and Jeou-Yuan Chen1,2

1 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China
2 Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan, Republic of China

Correspondence to Jeou-Yuan Chen: bmchen{at}ibms.sinica.edu.tw

Expression of the type I transmembrane glycoprotein CD44 has recently been recognized as a signature for cancer stem cells. In this study, we demonstrate that CD44, once engaged, is internalized and translocated to the nucleus, where it binds to various promoters, including that of cyclin D1, leading to cell fate change through transcriptional reprogramming. In regulating cyclin D1 expression, the internalized CD44 forms a complex with STAT3 and p300 (acetyltransferase), eliciting STAT3 acetylation at lysine 685 and dimer formation in a cytokine- and growth factor–independent manner. A bipartite nuclear localization signal (NLS) was mapped to the cytoplasmic tail of CD44, which mediates its nuclear translocation. Expression of CD44(NLS) mutant sequesters STAT3 in cytosol. In the nucleus, the acetylated STAT3 dimer remains associated with CD44 and binds to the cyclin D1 promoter, leading to increased cyclin D1 expression and cell proliferation. This study describes a novel function for CD44 in transcriptional modulation through nuclear translocation of the internalized CD44 and complex formation with transcription factors.

Abbreviations used in this paper: ChIP, chromatin IP; EMSA, electrophoretic mobility shift assay; H-3, Hermes-3; IP, immunoprecipitation; OPN, osteopontin; shRNA, short hairpin RNA; STAT, signal transducer and activator of transcription; WT, wild type.

© 2009 Lee et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article

CD44's nuclear road trip
Mitch Leslie
J. Cell Biol. 2009 185: 930. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents