Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10.
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.
Chen
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Ohio State Biochemistry Program, Ohio State University, Columbus, 43210, USA.
Wolfgang
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Hai
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D051700:Activating Transcription Factor 3; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000032:analysis* / Q000378:metabolism*
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP