Tiul1 and TGIF are Involved in Downregulation of TGFβ1-induced IgA Isotype Expression

다국어 초록 (Multilingual Abstract)

TGF-β1 is well known to induce Ig germ-line α (GLα) transcription
and subsequent IgA isotype class switching recombination
(CSR). Homeodomain protein TG-interacting
factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin
ligase 1 (Tiul1) are implicated in the negative regulation
of TGF-β signaling. In the present study, we investigated
the roles of Tiul1 and TGIF in TGFβ1-induced IgA CSR. We
found that over-expression of Tiul1 decreased TGFβ1-induced
GLα promoter activity and strengthened the inhibitory
effect of Smad7 on the promoter activity. Likewise,
overexpression of TGIF also diminished GLα promoter activity
and further strengthened the inhibitory effect of Tiul1,
suggesting that Tiul1 and TGIF can down-regulate TGFβ1-
induced GLα expression. In parallel, overexpression of Tiul1
decreased the expression of endogenous IgA CSR-predicitive
transcripts (GLTα, PSTα, and CTα) and TGFβ1-induced
IgA secretion, but not GLTγ3 and IgG3 secretion.
Here, over-expressed TGIF further strengthened the inhibitory
effect of Tiul1. These results suggest that Tiul1 and
TGIF act as negatively regulators in TGFβ1-induced IgA isotype
expression.

다국어 초록 (Multilingual Abstract)

TGF-β1 is well known to induce Ig germ-line α (GLα) transcription
and subsequent IgA isotype class switching recombination
(CSR). Homeodomain protein TG-interacting
factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin
ligase 1 (Tiul1) are implicated in the negative regulation
of TGF-β signaling. In the present study, we investigated
the roles of Tiul1 and TGIF in TGFβ1-induced IgA CSR. We
found that over-expression of Tiul1 decreased TGFβ1-induced
GLα promoter activity and strengthened the inhibitory
effect of Smad7 on the promoter activity. Likewise,
overexpression of TGIF also diminished GLα promoter activity
and further strengthened the inhibitory effect of Tiul1,
suggesting that Tiul1 and TGIF can down-regulate TGFβ1-
induced GLα expression. In parallel, overexpression of Tiul1
decreased the expression of endogenous IgA CSR-predicitive
transcripts (GLTα, PSTα, and CTα) and TGFβ1-induced
IgA secretion, but not GLTγ3 and IgG3 secretion.
Here, over-expressed TGIF further strengthened the inhibitory
effect of Tiul1. These results suggest that Tiul1 and
TGIF act as negatively regulators in TGFβ1-induced IgA isotype
expression.

참고문헌 (Reference)

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