Repression of Smad transcriptional activity by PIASy, an inhibitor of activated STAT

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

“…PIAS proteins inhibit STAT transcriptional activity by interfering with DNA binding via their NH 2 -terminal domains (14). PIAS proteins also recruit transcriptional corepressors such as histone deacetylases to target gene promoters to inhibit transcription (21,22). Furthermore, PIAS proteins influence the activation status of transcription factors by directly modifying the proteins themselves.…”

PIASy-Deficient Mice Display Modest Defects in IFN and Wnt Signaling

“…These include nuclear hormone receptors, such as the androgen receptor (AR), p53, Smad4, Sp3, HMGI-C, Gfi-1, IRF-1, TFII-I and yeast septins (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). In mouse and man, four Pias genes (Pias1, Pias3, Piasx, and Piasy) have been identified, which encode proteins that share a similar domain structure but differ in their specificity of interaction with other proteins.…”

“…PIAS1 and PIAS3 inhibit DNA binding of STAT1 and STAT3, respectively (1,2). In contrast, PIASy represses STAT1, LEF1, Smad4 and the AR without interfering with DNA binding by these proteins (3,24,26,27). The Piasx gene encodes two splice variants, x␣ (ARIP3) and x␤ (Miz1), which interact with the AR and with the homeodomain protein Msx2, respectively (28,29).…”

To (TGF)β or not to (TGF)β: Fine-tuning of Smad signaling via post-translational modifications

“…Thus, to some degree the effect of SUMOylation on Smad4 transcriptional activity may depend on the promoter and cell type, and even the SUMO E3 ligase involved. Interestingly, as well as exerting specificity in Smad4 SUMOylation, PIAS proteins can also have SUMOylationindependent functions in TGF-β signaling [79,80]. PIAS3 can form a complex with Smads and p300/CBP to activate Smad transcriptional activity [79], whereas PIASy can inhibit TGF-β/ Smad transcriptional responses through interactions with Smad proteins and histone deacetylase 1 (HDAC1) [80,81].…”

“…Interestingly, as well as exerting specificity in Smad4 SUMOylation, PIAS proteins can also have SUMOylationindependent functions in TGF-β signaling [79,80]. PIAS3 can form a complex with Smads and p300/CBP to activate Smad transcriptional activity [79], whereas PIASy can inhibit TGF-β/ Smad transcriptional responses through interactions with Smad proteins and histone deacetylase 1 (HDAC1) [80,81]. Thus, PIAS E3 ligases have dual regulatory effects on TGF-β signaling, and this must be taken into account when studying the effect of PIAS-mediated SUMOylation on the final cellular response to TGF-β superfamily ligands.…”