Regulation of Smad4 sumoylation and transforming growth factor-β signaling by protein inhibitor of activated STAT1
The tumor suppressor, Smad4/DPC4, is a common signal transducer in transforming growth factor-β (TGF-β) signaling. In this study, we demonstrated that the protein inhibitor of activated STAT1 (PIAS1) regulates the signaling potential of Smad4 through a sumoylation-dependent mechanism. PIAS1 was show...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 2004
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| In: |
The journal of biological chemistry
Year: 2004, Volume: 279, Issue: 22, Pages: 22857-22865 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M401554200 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1074/jbc.M401554200 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0021925820666467 
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| Author Notes: | Min Liang, Frauke Melchior, Xin-Hua Feng, and Xia Lin |
| Summary: | The tumor suppressor, Smad4/DPC4, is a common signal transducer in transforming growth factor-β (TGF-β) signaling. In this study, we demonstrated that the protein inhibitor of activated STAT1 (PIAS1) regulates the signaling potential of Smad4 through a sumoylation-dependent mechanism. PIAS1 was shown to be an E3 ligase for Smad4 sumoylation in vitro and in vivo. PIAS1 physically interacted with Smad4 in a TGF-β-inducible manner. A minimal SUMO E3 ligase domain and Smad4-binding domain were defined on PIAS1 protein. The RING finger domain of PIAS1 was essential for its E3 ligase function. Although PIAS1 enhanced the Smad4-dependent transcriptional activation of TGF-β signaling, a mutant lacking the RING domain inhibited the sumoylation of Smad4 in a dominant negative manner and, as a result, abolished the transcriptional response of TGF-β. These data demonstrate that PIAS1 protein positively modulates TGF-β responses as a SUMO E3 ligase for Smad4. |
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| Item Description: | Gesehen am 05.09.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M401554200 |