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-β (TGF-β). We have identified and characterized a splicing variant of smad3 . The splicing variant ( smad3 -Δ 3 ) lacks exon 3 resulting in a truncated linker region. We could detect mRNA expression of smad3 -Δ 3 in all investigated human tissues. Real-time PCR analyses demonstrated that the fraction of smad3 -Δ 3 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 -Δ 3 is overexpressed in a fibrosarcoma cell line, the Smad3-Δ3 is translocated to the nucleus upon TGF-β stimulation and binds the Smad responsive element. Using a CAGA luciferase reporter system, we demonstrate that Smad3-Δ3 has transcriptional activity and we conclude that Smad3-Δ3 possesses functional transactivating properties.