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PMID: 8622660 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10.

Molecular and cellular biology ·Vol. 16 ·No. 3 ·1996-03-00 ·Pages 1157-68

Chen BP, Wolfgang CD, Hai T

Abstract

We demonstrate that ATF3, a member of the ATF/CREB family of transcription factors, is induced in a variety of stressed tissues: mechanically injured liver, toxin-injured liver, blood-deprived heart, and postseizure brain. We also demonstrate that an ATF3-interacting protein, gadd153/Chop10, forms a nonfunctional heterodimer with ATF3: the heterodimer, in contrast to the ATF3 homodimer, does not bind to the ATF/cyclic AMP response element consensus site and does not repress transcription. Interestingly, ATF3 and gadd153/Chop10 are expressed in inverse but overlapping manners during the liver's response to carbon tetrachloride (CCl4): the level of gadd153/Chop10 mRNA is high in the normal liver and greatly decreases upon CCl4 treatment; the level of ATF3 mRNA, on the other hand, is low in the normal liver and greatly increases upon CCl4 treatment. We hypothesize that in nonstressed liver, gadd153/Chop10 inhibits the limited amount of ATF3 by forming an inactive heterodimer with it, whereas in CCl4-injured liver, the synthesis of gadd153/Chop10 is repressed, allowing the induced ATF3 to function.

MeSH Terms
Activating Transcription Factor 3 Animals Brain/metabolism,pathology CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins/metabolism Liver/metabolism,pathology Male Myocardium/metabolism,pathology RNA, Messenger/analysis Rats Rats, Sprague-Dawley Stress, Physiological Transcription Factor CHOP Transcription Factors/analysis,metabolism
Chemicals
Activating Transcription Factor 3 Atf3 protein, rat CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Ddit3 protein, rat RNA, Messenger Transcription Factors Transcription Factor CHOP
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen B P
Ohio State Biochemistry Program, Ohio State University, Columbus, 43210, USA.
Wolfgang C D
Hai T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1996-03-00
Pages
1157-68
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231098
Subset
IM
Grants
NIGMS NIH HHS · GM46218 · United States
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