JBC Advanced Glycation Endproducts

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on February 13, 2004
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
279/7/5278    most recent
M311517200v1
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Major, M. B.
Right arrow Articles by Jones, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Major, M. B.
Right arrow Articles by Jones, D. A.
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  
What's this?

Papers In Press, published online ahead of print November 20, 2003
J. Biol. Chem, 10.1074/jbc.M311517200
Submitted on October 21, 2003
Revised on November 19, 2003
Accepted on November 20, 2003

Identification of a Gadd45beta 3-prime enhancer that mediates SMAD3 and SMAD4 dependent transcriptional induction by TGFbeta

Michael B. Major and David A. Jones

Oncological Sciences, Huntsman Cancer Institute, Salt Lake City, UT 84112

Corresponding Author: david.jones{at}hci.utah.edu

Gadd45beta regulates cell growth, differentiation, and cell death following cellular exposure to diverse stimuli, including DNA damage and Transforming Growth Factor-beta (TGFbeta ). We examined how cells transduce the TGFbeta signal from the cell surface to the Gadd45beta genomic locus and describe how Gadd45beta contributes to TGFbeta biology. Following an alignment of Gadd45beta genomic sequences from multiple organisms, we discovered a novel TGFbeta -responsive enhancer encompassing the third intron of the Gadd45beta gene. Using three different experimental approaches, we found that SMAD3 and SMAD4, but not SMAD2, mediate transcription from this enhancer. Three lines of evidence support our conclusions. First, over-expression of SMAD3 and SMAD4 activated the transcriptional activity from this enhancer. Second, silencing of SMAD protein levels using short interfering RNAs revealed that TGFbeta -induced activation of the endogenous Gadd45beta gene required SMAD3 and SMAD4, but not SMAD2. In contrast, we found that the regulation of plasminogen activator inhibitor type I (PAI1) depended upon all three SMAD proteins. Lastly, SMAD3 and SMAD4 reconstitution in SMAD-deficient cancer cells restored TGFbeta induction of Gadd45beta . Finally, we assessed the function of Gadd45beta within the TGFbeta response and found that Gadd45beta deficient cells arrested in G2 following TGFbeta treatment. These data support a role for SMAD3 and SMAD4 in activating Gadd45beta through its third intron to facilitate G2 progression following TGFbeta treatment.


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    What's this?


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
M. J. Liguori, E. A.G. Blomme, and J. F. Waring
Trovafloxacin-Induced Gene Expression Changes in Liver-Derived in Vitro Systems: Comparison of Primary Human Hepatocytes to HepG2 Cells
Drug Metab. Dispos., February 1, 2008; 36(2): 223 - 233.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Kou, M. Nakajima, and S. Ikegawa
Expression and Regulation of the Osteoarthritis-associated Protein Asporin
J. Biol. Chem., November 2, 2007; 282(44): 32193 - 32199.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J.-A. Mendoza, Y. Jacob, P. Cassonnet, and M. Favre
Human Papillomavirus Type 5 E6 Oncoprotein Represses the Transforming Growth Factor {beta} Signaling Pathway by Binding to SMAD3
J. Virol., December 15, 2006; 80(24): 12420 - 12424.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Jazag, F. Kanai, H. Ijichi, K. Tateishi, T. Ikenoue, Y. Tanaka, M. Ohta, J. Imamura, B. Guleng, Y. Asaoka, et al.
Single small-interfering RNA expression vector for silencing multiple transforming growth factor-{beta} pathway components
Nucleic Acids Res., August 19, 2005; 33(15): e131 - e131.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.