Abstract
Zhangfei (ZF) is a basic region-leucine zipper protein that has been implicated in herpesvirus infection cycle and related cellular processes. Here we show both in vivo and in vitro data demonstrating that ZF is a novel cellular binding partner of activating transcription factor 4 (ATF4) (or CREB2). We found that ZF competed with ATF4 to form ATF4-ZF heterodimeric complexes through the bZIP regions. ZF enhanced ATF4 binding to the cAMP response element (CRE), and augmented activation of a CRE reporter by ATF4, in response to MEK1 activation. These results suggest an important role of ZF in the MEK1-ATF4 signaling pathway.
MeSH terms
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Activating Transcription Factor 4 / genetics
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Activating Transcription Factor 4 / metabolism*
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism*
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Cyclic AMP / metabolism
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HeLa Cells
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Herpesviridae / genetics
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Herpesviridae / metabolism
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Herpesviridae Infections / genetics
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Herpesviridae Infections / metabolism
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Humans
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MAP Kinase Kinase 1 / genetics
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MAP Kinase Kinase 1 / metabolism*
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MAP Kinase Signaling System / physiology*
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Nuclear Proteins
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Protein Structure, Tertiary / physiology
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RNA-Binding Proteins
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Response Elements / physiology*
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Transcription Factors
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Virus Replication / physiology
Substances
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ALYREF protein, human
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ATF4 protein, human
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Basic-Leucine Zipper Transcription Factors
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CREBZF protein, human
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Nuclear Proteins
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RNA-Binding Proteins
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Transcription Factors
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Activating Transcription Factor 4
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Cyclic AMP
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MAP Kinase Kinase 1
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MAP2K1 protein, human