| Dickkopf homolog 1, a Wnt signaling antagonist, is transcriptionally up-regulated via an ATF4-independent and MAPK/ERK-dependent pathway following amino acid deprivation. | |
| | |
MedLine Citation:
|
PMID: 21683813 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Amino acid response (AAR) pathway is activated when cells are deprived of amino acids. In the present study, using the human colon cancer cell line SW480, we observed that DKK1, an antagonist of the Wnt pathway, was significantly induced at the mRNA level after the removal of amino acids from the medium. Addition of the amino alcohol histidinol, which prevents the formation of histidinyl-tRNA(His), also increased DKK1 mRNA to a level similar to that observed when cells were deprived of all amino acids. Transcriptional activity and stability of DKK1 mRNA were both increased in the amino acid-deprived condition. The induction of DKK1 gene expression was confirmed by the increased immunofluorescent staining of the DKK1 protein in the amino acid deprived condition. Although chromatin immunoprecipitation assays showed increased RNA Polymerase II binding at the DKK1 promoter in amino acid-limited conditions, ATF4 binding to the promoter is absent. Luciferase reporter assays did not detect any functional AARE within the DKK1 gene structure. Knockdown of ATF4 by siRNA did not affect the increase of DKK1 mRNA during amino acid limitation. Inhibition of ERK phosphorylation abolished the induction of DKK1. Our study revealed that DKK1 is a novel target gene in the response to amino acid deficiency and that the expression of DKK1 is up-regulated through an ATF4-independent and an ERK-dependent pathway. |
| | |
Authors:
|
Dan Zhou; Yukun Zhang; Yuan-Xiang Pan; Hong Chen |
Related Documents
:
|
345733 - A double-blind study of the influence of tranexamic acid on the central corneal thickne... 16507623 - Valproic acid management of acute alcohol withdrawal. 22682363 - Volatile organic compounds at swine facilities: a critical review. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-06-13 |
Journal Detail:
|
Title: Biochimica et biophysica acta Volume: 1809 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-08-01 Completed Date: 2011-09-20 Revised Date: 2012-07-04 |
Medline Journal Info:
|
Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 306-15 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 Elsevier B.V. All rights reserved. |
Affiliation:
|
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Activating Transcription Factor 4
/
genetics,
metabolism* Amino Acids Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases / genetics, metabolism Humans Intercellular Signaling Peptides and Proteins / biosynthesis*, genetics MAP Kinase Signaling System / physiology* Phosphorylation / physiology Promoter Regions, Genetic / physiology RNA Polymerase II / genetics, metabolism Transcription, Genetic / physiology* Up-Regulation / physiology* Wnt Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
R03 CA135262-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/ATF4 protein, human; 0/Amino Acids; 0/DKK1 protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/Wnt Proteins; 145891-90-3/Activating Transcription Factor 4; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.7.-/RNA Polymerase II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The nuclear exporter, Crm1, is regulated by NFY and Sp1 in cancer cells and repressed by p53 in resp...
Next Document: Drosha processing controls the specificity and efficiency of global microRNA expression.