An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli.
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.
Hashimoto
Yoshinori
Y
Department of Biochemical Genetics, Medical Research Institute and Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Zhang
Chun
C
Kawauchi
Junya
J
Imoto
Issei
I
Adachi
Mimi T
MT
Inazawa
Johji
J
Amagasa
Teruo
T
Hai
Tsonwin
T
Kitajima
Shigetaka
S
D051700:Activating Transcription Factor 3; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D051700:Activating Transcription Factor 3; D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D014415:Tunicamycin; D000001:Calcimycin; D019284:Thapsigargin; D004247:DNA; D006861:Hydrogen Peroxide