TY - JOUR
T1 - Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)
AU - Long, Jianyin
AU - Wang, Guannan
AU - Matsuura, Isao
AU - He, Dongming
AU - Liu, Fang
PY - 2004/1
Y1 - 2004/1
N2 - Smad proteins play pivotal roles in mediating the transforming growth factor β (TGF-β) transcriptional responses. We show in this report that PIAS3, a member of the protein inhibitor of activated STAT (PIAS) family, activates TGF-β/Smad transcriptional responses. PIAS3 interacts with Smad proteins, most strongly with Smad3. PIAS3 and Smad3 interact with each other at the endogenous protein level in mammalian cells and also in vitro, and the association occurs through the C-terminal domain of Smad3. We further show that PIAS3 can interact with the general coactivators p300/CBP, the first evidence that a PIAS protein can associate with p300/CBP. In contrast, PIASy, which inhibits Smad transcriptional activity and other transcriptional responses, is unable to interact with p300/CBP. The RING domain of PIAS3 is essential for interaction with p300/CBP, and a RING domain mutant PIAS3, which cannot bind p300/CBP, no longer activates TGF-β/Smad-dependent transcription. Furthermore, we show that PIAS3, Smad3, and p300 can form a ternary complex, which is markedly increased by TGF-β treatment. Taken together, our studies indicate that on TGF-β treatment, PIAS3 can form a complex with Smads and p300/CBP and activate Smad transcriptional activity.
AB - Smad proteins play pivotal roles in mediating the transforming growth factor β (TGF-β) transcriptional responses. We show in this report that PIAS3, a member of the protein inhibitor of activated STAT (PIAS) family, activates TGF-β/Smad transcriptional responses. PIAS3 interacts with Smad proteins, most strongly with Smad3. PIAS3 and Smad3 interact with each other at the endogenous protein level in mammalian cells and also in vitro, and the association occurs through the C-terminal domain of Smad3. We further show that PIAS3 can interact with the general coactivators p300/CBP, the first evidence that a PIAS protein can associate with p300/CBP. In contrast, PIASy, which inhibits Smad transcriptional activity and other transcriptional responses, is unable to interact with p300/CBP. The RING domain of PIAS3 is essential for interaction with p300/CBP, and a RING domain mutant PIAS3, which cannot bind p300/CBP, no longer activates TGF-β/Smad-dependent transcription. Furthermore, we show that PIAS3, Smad3, and p300 can form a ternary complex, which is markedly increased by TGF-β treatment. Taken together, our studies indicate that on TGF-β treatment, PIAS3 can form a complex with Smads and p300/CBP and activate Smad transcriptional activity.
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U2 - 10.1073/pnas.0307598100
DO - 10.1073/pnas.0307598100
M3 - Article
C2 - 14691252
AN - SCOPUS:0347719405
SN - 0027-8424
VL - 101
SP - 99
EP - 104
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -