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

Gene. 2004 Mar 3;327(2):141-52. doi: 10.1016/j.gene.2003.11.026.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Electrophoretic Mobility Shift Assay
  • Female
  • Gene Expression Profiling
  • Genetic Variation
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcriptional Activation
  • Transforming Growth Factor beta / pharmacology


  • 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