Identification and characterization of a human smad3 splicing variant lacking part of the linker region.

Abstract	Smad3 is one of the signal transducers that are activated in response to transforming growth factor-beta (TGF-beta). We have identified and characterized a splicing variant of smad3. The splicing variant (smad3-Delta3) lacks exon 3 resulting in a truncated linker region. We could detect mRNA expression of smad3-Delta3 in all investigated human tissues. Real-time PCR analyses demonstrated that the fraction of smad3-Delta3 mRNA compared to normal smad3 varies between tissues. The amount of spliced mRNA was estimated to represent 0.5-5% of the normal smad3 mRNA. When smad3-Delta3 is overexpressed in a fibrosarcoma cell line, the Smad3-Delta3 is translocated to the nucleus upon TGF-beta stimulation and binds the Smad responsive element. Using a CAGA luciferase reporter system, we demonstrate that Smad3-Delta3 has transcriptional activity and we conclude that Smad3-Delta3 possesses functional transactivating properties.
Authors	Christian Kjellman, Gabriella Honeth, Sofia Järnum, Magnus Lindvall, Anna Darabi, Ingar Nilsson, Klaus Edvardsen, Leif G Salford, Bengt Widegren
Journal	Gene (Gene) Vol. 327 Issue 2 Pg. 141-52 (Mar 03 2004) ISSN: 0378-1119 [Print] Netherlands
PMID	14980711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins RNA, Messenger Recombinant Fusion Proteins SMAD3 protein, human SMAD4 protein, human Smad3 Protein Smad4 Protein Trans-Activators Transforming Growth Factor beta Luciferases
Topics	Alternative Splicing Amino Acid Sequence Animals Base Sequence COS Cells Cell Line Cell Line, Tumor Cell Nucleus (metabolism) Chlorocebus aethiops DNA-Binding Proteins (genetics, metabolism) Electrophoretic Mobility Shift Assay Female Gene Expression Profiling Genetic Variation Humans Luciferases (genetics, metabolism) Molecular Sequence Data Protein Binding Protein Transport (drug effects) RNA, Messenger (genetics, metabolism) Recombinant Fusion Proteins (genetics, metabolism) Sequence Deletion Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Smad3 Protein Smad4 Protein Trans-Activators (genetics, metabolism) Transcriptional Activation Transforming Growth Factor beta (pharmacology)

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