Abstract
Activating transcription factor 3 (ATF3) is a member of the ATF/CREB family of transcription factors and its expression is increased by various pathophysiological conditions and in several cancer cells. In this study, we describe two alternatively spliced ATF3DeltaZip mRNAs: ATF3DeltaZip2a and ATF3DeltaZip2b. Both variants encoded the same truncated protein of 135 amino acids, which lacked the leucine zipper domain and was incapable of binding to the ATF/CRE motif. The ATF3DeltaZip2 protein was shown to be localized in the nuclei and counteracted the transcriptional repression by the full-length ATF3. Western blot analysis showed that ATF3DeltaZip2 was expressed in cells exposed to A23187. Further study showed that, similar to the full-length ATF3, the expression of ATF3DeltaZip2 was induced by a wide range of stress stimuli. However, its expression was not detectable in cancer cells that constitutively over-expressed ATF3. Taken together, our results suggest that ATF3DeltaZip2, a protein derived from alternatively spliced mRNAs, is induced by various stress signals and may modulate the activity of the full-length ATF3 protein during stress response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activating Transcription Factor 3
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Alternative Splicing / genetics*
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Animals
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Calcimycin / pharmacology
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Cell Nucleus / metabolism
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Cells, Cultured
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Cloning, Molecular
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DNA / genetics
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DNA / metabolism
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Homocysteine / pharmacology
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Humans
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Hydrogen Peroxide / pharmacology
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Mice
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Molecular Sequence Data
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Oxidative Stress* / drug effects
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Protein Isoforms / biosynthesis
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Transport
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Repressor Proteins / biosynthesis*
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Repressor Proteins / chemistry
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Thapsigargin / pharmacology
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Transcription Factors / biosynthesis*
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Transcription Factors / chemistry
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology
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Tunicamycin / pharmacology
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Up-Regulation* / drug effects
Substances
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Activating Transcription Factor 3
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Protein Isoforms
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RNA, Messenger
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Repressor Proteins
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Transcription Factors
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Tumor Necrosis Factor-alpha
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Homocysteine
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Tunicamycin
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Calcimycin
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Thapsigargin
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DNA
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Hydrogen Peroxide
Associated data
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GENBANK/AB078026
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GENBANK/AB078027